Pub Date : 2024-12-01DOI: 10.1016/j.mcp.2024.101994
Fei Li, Wenwen Han, Hailong Sun
Background
Low-dose spiral CT imaging has been employed for cancer diagnosis, but its sensitivity and specificity were unsatisfactory. MicroRNAs have been considered an approach for screening cancers, and the function of miR-155–5p in lung cancer has been previously revealed.
Objectives
This study assessed the diagnostic value of combining low-dose spiral CT with serum miR-155–5p in lung cancer aiming to explore a novel strategy to assist the clinical cancer diagnosis.
Methods
This study enrolled 115 lung cancer patients and 115 patients with benign lung diseases as control. All patients received low-dose spiral CT imaging, and serum miR-155–5p levels were analyzed by PCR. The diagnostic potential of miR-155–5p in lung cancer was evaluated by receiver operating curve (ROC), and its significance in evaluating the risk of lung cancer was evaluated by logistic regression analysis. The consistency of serum miR-155–5p and low-dose spiral CT imaging with pathological examination was assessed by the Kappa test.
Results
Reduced serum miR-155–5p indicated the risk of lung cancer in patients with benign lung diseases. Decreased serum miR-155–5p showed significant diagnostic value in early lung cancer and was significantly associated with disease severity. Low-dose spiral CT imaging showed significant diagnostic value in early lung cancer and showed middle consistency with pathological examination. Combining low-dose spiral CT imaging with serum miR-155–5p improved the diagnostic sensitivity and accuracy in early lung cancer, reduced the false positive rate, and showed better consistency with pathological examination.
Conclusion
Serum miR-155–5p levels could assist the early detection of lung cancer by low-dose spiral CT examination.
{"title":"Serum miR-155–5p assists the diagnostic sensitivity and accuracy of low-dose spiral CT imaging in early lung cancer","authors":"Fei Li, Wenwen Han, Hailong Sun","doi":"10.1016/j.mcp.2024.101994","DOIUrl":"10.1016/j.mcp.2024.101994","url":null,"abstract":"<div><h3>Background</h3><div>Low-dose spiral CT imaging has been employed for cancer diagnosis, but its sensitivity and specificity were unsatisfactory. MicroRNAs have been considered an approach for screening cancers, and the function of miR-155–5p in lung cancer has been previously revealed.</div></div><div><h3>Objectives</h3><div>This study assessed the diagnostic value of combining low-dose spiral CT with serum miR-155–5p in lung cancer aiming to explore a novel strategy to assist the clinical cancer diagnosis.</div></div><div><h3>Methods</h3><div>This study enrolled 115 lung cancer patients and 115 patients with benign lung diseases as control. All patients received low-dose spiral CT imaging, and serum miR-155–5p levels were analyzed by PCR. The diagnostic potential of miR-155–5p in lung cancer was evaluated by receiver operating curve (ROC), and its significance in evaluating the risk of lung cancer was evaluated by logistic regression analysis. The consistency of serum miR-155–5p and low-dose spiral CT imaging with pathological examination was assessed by the Kappa test.</div></div><div><h3>Results</h3><div>Reduced serum miR-155–5p indicated the risk of lung cancer in patients with benign lung diseases. Decreased serum miR-155–5p showed significant diagnostic value in early lung cancer and was significantly associated with disease severity. Low-dose spiral CT imaging showed significant diagnostic value in early lung cancer and showed middle consistency with pathological examination. Combining low-dose spiral CT imaging with serum miR-155–5p improved the diagnostic sensitivity and accuracy in early lung cancer, reduced the false positive rate, and showed better consistency with pathological examination.</div></div><div><h3>Conclusion</h3><div>Serum miR-155–5p levels could assist the early detection of lung cancer by low-dose spiral CT examination.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"78 ","pages":"Article 101994"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.mcp.2024.101995
Jun Li , Shuxin Ding , Min Li , Bo Zou , Miaomiao Chu , Guohao Gu , Cheng Chen , Yu-jiao Liu , Ke Zheng , Zhen Meng
Oral squamous cell carcinoma (OSCC), one of the most common types of head and neck squamous cell carcinoma (HNSCC), is characterized by high incidence and mortality. PVT1 is a long non-coding RNA (lncRNA) that plays an oncogenic role in various cancer types. This study aims to reveal the role and underlying molecular mechanism of PVT1 in OSCC progression. The expression levels of PVT1, miR-7-5p, and CDKL1 mRNA were evaluated using qRT-PCR. Western blot and IHC analysis were conducted to determine the protein expression of CDKL1. The biological functions of PVT1, miR-7-5p, and CDKL1 in OSCC were investigated through CCK-8, transwell migration and invasion assays. In vivo experiments utilized a xenograft model to examine the impact of PVT1 on OSCC. Furthermore, the interaction among PVT1, miR-7-5p, and CDKL1 was explored using RNA pull down assay and luciferase reporter assays. We found that PVT1 enhanced cell proliferation, migration, and invasion by targeting CDKL1. In addition, PVT1 functions as a sponge to modulate miR-7-5p, thereby influencing the expression of CDKL1 and the progression of OSCC. In conclusion, this study illustrates that the "PVT1/miR-7-5p/CDKL1" pathway is capable of promoting the progression of OSCC and may serve as a promising target for developing treatment strategies for OSCC.
{"title":"LncRNA PVT1 promotes malignant progression by regulating the miR-7-5p/CDKL1 axis in oral squamous cell carcinoma","authors":"Jun Li , Shuxin Ding , Min Li , Bo Zou , Miaomiao Chu , Guohao Gu , Cheng Chen , Yu-jiao Liu , Ke Zheng , Zhen Meng","doi":"10.1016/j.mcp.2024.101995","DOIUrl":"10.1016/j.mcp.2024.101995","url":null,"abstract":"<div><div>Oral squamous cell carcinoma (OSCC), one of the most common types of head and neck squamous cell carcinoma (HNSCC), is characterized by high incidence and mortality. PVT1 is a long non-coding RNA (lncRNA) that plays an oncogenic role in various cancer types. This study aims to reveal the role and underlying molecular mechanism of PVT1 in OSCC progression. The expression levels of PVT1, miR-7-5p, and CDKL1 mRNA were evaluated using qRT-PCR. Western blot and IHC analysis were conducted to determine the protein expression of CDKL1. The biological functions of PVT1, miR-7-5p, and CDKL1 in OSCC were investigated through CCK-8, transwell migration and invasion assays. In vivo experiments utilized a xenograft model to examine the impact of PVT1 on OSCC. Furthermore, the interaction among PVT1, miR-7-5p, and CDKL1 was explored using RNA pull down assay and luciferase reporter assays. We found that PVT1 enhanced cell proliferation, migration, and invasion by targeting CDKL1. In addition, PVT1 functions as a sponge to modulate miR-7-5p, thereby influencing the expression of CDKL1 and the progression of OSCC. In conclusion, this study illustrates that the \"PVT1/miR-7-5p/CDKL1\" pathway is capable of promoting the progression of OSCC and may serve as a promising target for developing treatment strategies for OSCC.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"78 ","pages":"Article 101995"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-10-13DOI: 10.1016/j.mcp.2024.101986
Bashdar Mahmud Hussen, Mohammed Fatih Rasul, Goran Sedeeq Hama Faraj, Snur Rasool Abdullah, Seerwan Hamadameen Sulaiman, Hasan Pourmoshtagh, Mohammad Taheri
Active neutrophils play a variety of roles in both innate and adaptive immune responses, and one of the most vital roles is the formation and release of neutrophil extracellular traps (NETs). NETs are created when neutrophils release their chromatin contents to get and eradicate pathogenic organisms essentially. While NET helps fight bacteria, viruses, parasites, and infections, it is also linked to asthma, atherosclerosis, and cancer metastasis. Thus, understanding the molecular mechanisms behind NETosis formation and its inhibition is crucial for developing safe and effective therapies. This systematic review aims to identify the list of miRNAs that are associated with the formation of NETosis and illustrate the mechanism of action by classifying them based on their expression site. Moreover, it summarizes the list of miRNAs that can be targeted therapeutically to reduce NETosis in various disorders. The current study entailed the searching of PubMed and Google Scholar for articles related to the research topic role of miRNAs in NETosis in all types of disorders. The search terms and phrases included "NETs," "neutrophil extracellular traps," "NETosis," "miRNA," "miR," and "micro-RNA." The search was limited to articles published in English since October 2024 in both databases. Following a review of 23 papers, 19 of them met the inclusion and exclusion criteria of this study. Four papers have been removed as they are duplicated or do not meet our criteria. According to the published articles till October 2024, there are 14 miRNAs involved in the molecular pathway of NETosis which are miR-155, miR-1696, miR-7, miR-223, miR-146a, miR-142a-3p, miR-3146, miR-505, miR-4512, miR-15b-5p, miR-16-5p, miR-26b-5p, miR-125a-3p and miR-378a-3p. Moreover, eight miRNAs have been identified as possible therapeutic targets for the suppression of NETosis based on in-vivo studies carried out in various organisms, which are miR-155, miR-146a, miR-1696, miR-223, miR-142a-3p, miR-3146, miR-4512, miR-16-5p. Different miRNAs that are expressed inside or outside of neutrophils can regulate and influence NETosis. Eight miRNAs have also been identified as potential therapeutic targets, which can be utilized to inhibit the molecular pathways associated with NETosis and prevent its negative effects, such as asthma, atherosclerosis, cancer metastasis, and cancer recurrence. However, further human-based research is necessary to completely understand the role of miRNAs in the development of NETosis in humans.
{"title":"Role of microRNAs in neutrophil extracellular trap formation and prevention: Systematic narrative review.","authors":"Bashdar Mahmud Hussen, Mohammed Fatih Rasul, Goran Sedeeq Hama Faraj, Snur Rasool Abdullah, Seerwan Hamadameen Sulaiman, Hasan Pourmoshtagh, Mohammad Taheri","doi":"10.1016/j.mcp.2024.101986","DOIUrl":"10.1016/j.mcp.2024.101986","url":null,"abstract":"<p><p>Active neutrophils play a variety of roles in both innate and adaptive immune responses, and one of the most vital roles is the formation and release of neutrophil extracellular traps (NETs). NETs are created when neutrophils release their chromatin contents to get and eradicate pathogenic organisms essentially. While NET helps fight bacteria, viruses, parasites, and infections, it is also linked to asthma, atherosclerosis, and cancer metastasis. Thus, understanding the molecular mechanisms behind NETosis formation and its inhibition is crucial for developing safe and effective therapies. This systematic review aims to identify the list of miRNAs that are associated with the formation of NETosis and illustrate the mechanism of action by classifying them based on their expression site. Moreover, it summarizes the list of miRNAs that can be targeted therapeutically to reduce NETosis in various disorders. The current study entailed the searching of PubMed and Google Scholar for articles related to the research topic role of miRNAs in NETosis in all types of disorders. The search terms and phrases included \"NETs,\" \"neutrophil extracellular traps,\" \"NETosis,\" \"miRNA,\" \"miR,\" and \"micro-RNA.\" The search was limited to articles published in English since October 2024 in both databases. Following a review of 23 papers, 19 of them met the inclusion and exclusion criteria of this study. Four papers have been removed as they are duplicated or do not meet our criteria. According to the published articles till October 2024, there are 14 miRNAs involved in the molecular pathway of NETosis which are miR-155, miR-1696, miR-7, miR-223, miR-146a, miR-142a-3p, miR-3146, miR-505, miR-4512, miR-15b-5p, miR-16-5p, miR-26b-5p, miR-125a-3p and miR-378a-3p. Moreover, eight miRNAs have been identified as possible therapeutic targets for the suppression of NETosis based on in-vivo studies carried out in various organisms, which are miR-155, miR-146a, miR-1696, miR-223, miR-142a-3p, miR-3146, miR-4512, miR-16-5p. Different miRNAs that are expressed inside or outside of neutrophils can regulate and influence NETosis. Eight miRNAs have also been identified as potential therapeutic targets, which can be utilized to inhibit the molecular pathways associated with NETosis and prevent its negative effects, such as asthma, atherosclerosis, cancer metastasis, and cancer recurrence. However, further human-based research is necessary to completely understand the role of miRNAs in the development of NETosis in humans.</p>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":" ","pages":"101986"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.mcp.2024.101993
Qi Song, Lina He, Jing Feng
Background
The prognosis of advanced osteosarcoma (OS) has remained stagnant in last decades, requiring the identification of novel therapeutic targets. Recently, much attention was paid to the role of squalene epoxidase (SQLE), a rate-limiting enzyme in cholesterol metabolism, in the field of oncology, while the specific role of SQLE in OS has not been sufficiently elucidated. The present study aims to investigate the role of SQLE in the progression of OS and explore the potential mechanisms.
Methods
The expression levels of SQLE in OS tissues and adjacent normal tissues were compared using bioinformatic methods and experiments. Kaplan-Meier survival analysis and univariate and multivariate Cox analysis were performed to detect the association of SQLE expression and patient’ prognosis. Stably cell lines with SQLE knockdown or overexpression were constructed by lentivirus infection. CCK-8, colony formation, scratch healing, and Transwell invasion assays were carried out to explore the effect of SQLE knockdown or overexpression on the proliferation, migration, and invasion of OS cells. Gene set enrichment analysis was conducted to reveal signaling pathways associated with SQLE expression. The effect of SQLE on TGFβ/SMAD signaling pathway were explored by Western blot assay.
Results
Here, we found a notable rise of SQLE expression in OS tissues and cell lines. Survival analysis showed that individuals with high SQLE expression had a lower median overall survival time compared to those with low SQLE expression. Univariate and multivariate Cox regression analyses showed that SQLE might have the potency to serve as an independently prognostic biomarker in OS. Loss- and gain-of-function experiments indicated that silence of SQLE suppressed OS cell proliferation, migration, and invasion, while overexpression of SQLE exerted the opposite effects. Mechanistically, TGF-β signaling pathway was identified as the downstream pathway of SQLE through bioinformatic methods, and the results of Western blot assay showed that SQLE positively regulated the activity of TGFβ1/SMAD2/3 signaling in OS. Resue experiments demonstrated that SB431542, a small molecule that inhibits TGFβ/SMAD signaling, could partly reverse the promoting effects of SQLE on OS cell proliferation, migration, and invasion.
Conclusion
Our results provided preliminary evidences that SQLE was a tumor-promoting factor and prognosis predictor in OS. SQLE promoted OS cell proliferation, migration, and invasion via activating TGFβ/SMAD signaling and targeting SQLE might be a potential strategy for the treatment of OS.
{"title":"SQLE promotes osteosarcoma progression via activating TGFβ/SMAD signaling pathway","authors":"Qi Song, Lina He, Jing Feng","doi":"10.1016/j.mcp.2024.101993","DOIUrl":"10.1016/j.mcp.2024.101993","url":null,"abstract":"<div><h3>Background</h3><div>The prognosis of advanced osteosarcoma (OS) has remained stagnant in last decades, requiring the identification of novel therapeutic targets. Recently, much attention was paid to the role of squalene epoxidase (SQLE), a rate-limiting enzyme in cholesterol metabolism, in the field of oncology, while the specific role of SQLE in OS has not been sufficiently elucidated. The present study aims to investigate the role of SQLE in the progression of OS and explore the potential mechanisms.</div></div><div><h3>Methods</h3><div>The expression levels of SQLE in OS tissues and adjacent normal tissues were compared using bioinformatic methods and experiments. Kaplan-Meier survival analysis and univariate and multivariate Cox analysis were performed to detect the association of SQLE expression and patient’ prognosis. Stably cell lines with SQLE knockdown or overexpression were constructed by lentivirus infection. CCK-8, colony formation, scratch healing, and Transwell invasion assays were carried out to explore the effect of SQLE knockdown or overexpression on the proliferation, migration, and invasion of OS cells. Gene set enrichment analysis was conducted to reveal signaling pathways associated with SQLE expression. The effect of SQLE on TGFβ/SMAD signaling pathway were explored by Western blot assay.</div></div><div><h3>Results</h3><div>Here, we found a notable rise of SQLE expression in OS tissues and cell lines. Survival analysis showed that individuals with high SQLE expression had a lower median overall survival time compared to those with low SQLE expression. Univariate and multivariate Cox regression analyses showed that SQLE might have the potency to serve as an independently prognostic biomarker in OS. Loss- and gain-of-function experiments indicated that silence of SQLE suppressed OS cell proliferation, migration, and invasion, while overexpression of SQLE exerted the opposite effects. Mechanistically, TGF-β signaling pathway was identified as the downstream pathway of SQLE through bioinformatic methods, and the results of Western blot assay showed that SQLE positively regulated the activity of TGFβ1/SMAD2/3 signaling in OS. Resue experiments demonstrated that SB431542, a small molecule that inhibits TGFβ/SMAD signaling, could partly reverse the promoting effects of SQLE on OS cell proliferation, migration, and invasion.</div></div><div><h3>Conclusion</h3><div>Our results provided preliminary evidences that SQLE was a tumor-promoting factor and prognosis predictor in OS. SQLE promoted OS cell proliferation, migration, and invasion via activating TGFβ/SMAD signaling and targeting SQLE might be a potential strategy for the treatment of OS.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"78 ","pages":"Article 101993"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The metabotropic glutamate receptor, GRM7 is a gene in the neurotransmitters prognostic signatures. Downregulation of this gene is associated with the progression of glioma tumors and has a negative impact on the immune response.
Methods
In the present study, we aim to assess the associations between rs6782011 and rs779867 SNPs within this gene and risk of glioblastoma multiforme (GBM) in Iranian population.
Results
There was a noteworthy difference in distribution of genotypes (P value = 0.001) and alleles (P value = 0.0002) of rs779867 between total GBM cases (n = 299) and total normal controls (n = 302). In addition, the significant difference in genotypes and alleles distribution was observed for both male and female GBM cases vs. respective normal controls. For rs6782011 variant, the significant difference in genotypes distribution was observed between male GBM cases (n = 187) vs. respective normal controls (n = 156) (P value = 0.004) and between total GBM cases (n = 299) vs. total normal controls (n = 302) (P value = 0.02). However, there was no significant difference in genotypes distribution between female GBM cases and respective normal controls (P value = 0.1). Distribution of rs6782011 alleles was not different between total GBM cases and normal controls; and between male GBM cases and male normal controls. However, there was a significant difference in alleles distribution between female GBM cases and female normal controls. Conclusion: Taken together, the mentioned polymorphisms might affect risk of GBM in Iranian population. Future studies are needed to elaborate the underlying mechanism.
{"title":"Impact of GRM7 gene variations on glioblastoma risk in the Iranian population","authors":"Elena Jamali , Atefeh Harsij , Mohammadamin Yarahmadi , Farahnaz Bidari-Zerehpoush , Yasaman Gholinezhad , Solat Eslami , Hossein Farahzadi , Fariba Agahi , Mohadeseh Fathi , Soudeh Ghafouri-Fard , Mohammad Samadian","doi":"10.1016/j.mcp.2024.101996","DOIUrl":"10.1016/j.mcp.2024.101996","url":null,"abstract":"<div><h3>Aim</h3><div>The metabotropic glutamate receptor, <em>GRM7</em> is a gene in the neurotransmitters prognostic signatures. Downregulation of this gene is associated with the progression of glioma tumors and has a negative impact on the immune response.</div></div><div><h3>Methods</h3><div>In the present study, we aim to assess the associations between rs6782011 and rs779867 SNPs within this gene and risk of glioblastoma multiforme (GBM) in Iranian population.</div></div><div><h3>Results</h3><div>There was a noteworthy difference in distribution of genotypes (P value = 0.001) and alleles (P value = 0.0002) of rs779867 between total GBM cases (n = 299) and total normal controls (n = 302). In addition, the significant difference in genotypes and alleles distribution was observed for both male and female GBM cases vs. respective normal controls. For rs6782011 variant, the significant difference in genotypes distribution was observed between male GBM cases (n = 187) vs. respective normal controls (n = 156) (P value = 0.004) and between total GBM cases (n = 299) vs. total normal controls (n = 302) (P value = 0.02). However, there was no significant difference in genotypes distribution between female GBM cases and respective normal controls (P value = 0.1). Distribution of rs6782011 alleles was not different between total GBM cases and normal controls; and between male GBM cases and male normal controls. However, there was a significant difference in alleles distribution between female GBM cases and female normal controls. <strong>Conclusion</strong>: Taken together, the mentioned polymorphisms might affect risk of GBM in Iranian population. Future studies are needed to elaborate the underlying mechanism.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"78 ","pages":"Article 101996"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-25DOI: 10.1016/j.mcp.2024.101990
Weiwei Ning, Qingxu Yang, Zhengbiao Li, Ming Xie
In gastric cancer (GC), tumor cell metastasis to lymph node may occur, and can be impacted by synaptojanin 2 (SYNJ2). Herein, we explored the mechanism of SYNJ2 in the progress of GC. SYNJ2 level in GC tissues was predicted by GEPIA database. After GC cells were transfected with short hairpin RNA against SYNJ2 (shSYNJ2), shGRB2, SYNJ2 overexpression plasmid and growth factor receptor-bound protein 2 (GRB2) overexpression plasmid, the mRNA levels of SYNJ2 and GRB2 in GC cells were quantified by qRT-PCR. CCK-8, flow cytometry, wound healing, transwell and tube formation assays were performed for detecting viability, apoptosis, migration, invasion and angiogenesis of GC cells. Protein levels of GRB2, vascular endothelial growth factor (VEGF), E-Cadherin, N-Cadherin and Vimentin in GC cells were measured by Western blot. The relationship between SYNJ2 and GRB2 was assessed by Co-immunoprecipitation (CO-IP) assay. SYNJ2 was highly expressed in GC tissues and cells. SYNJ2 overexpression promoted viability, migration, invasion, angiogenesis and GRB2 level, and inhibited apoptosis of GC cells, while shSYNJ2 exhibited opposite effects. GRB2 overexpression boosted yet shGRB2 suppressed cell migration, invasion and angiogenesis. Notably, SYNJ2 could interact with GRB2. GRB2 overexpression and shGRB2 reversed the effects of shSYNJ2 and overexpressed SYNJ2 on cell migration, invasion and angiogenesis and levels of metastasis-related proteins, respectively. In conclusion, SYNJ2 promotes GC cell metastasis and angiogenesis by up-regulating GRB2.
{"title":"The activation of SYNJ2/GRB2 axis accelerates the malignant metastasis and angiogenesis of gastric cancer cells","authors":"Weiwei Ning, Qingxu Yang, Zhengbiao Li, Ming Xie","doi":"10.1016/j.mcp.2024.101990","DOIUrl":"10.1016/j.mcp.2024.101990","url":null,"abstract":"<div><div>In gastric cancer (GC), tumor cell metastasis to lymph node may occur, and can be impacted by synaptojanin 2 (SYNJ2). Herein, we explored the mechanism of SYNJ2 in the progress of GC. SYNJ2 level in GC tissues was predicted by GEPIA database. After GC cells were transfected with short hairpin RNA against SYNJ2 (shSYNJ2), shGRB2, SYNJ2 overexpression plasmid and growth factor receptor-bound protein 2 (GRB2) overexpression plasmid, the mRNA levels of SYNJ2 and GRB2 in GC cells were quantified by qRT-PCR. CCK-8, flow cytometry, wound healing, transwell and tube formation assays were performed for detecting viability, apoptosis, migration, invasion and angiogenesis of GC cells. Protein levels of GRB2, vascular endothelial growth factor (VEGF), E-Cadherin, N-Cadherin and Vimentin in GC cells were measured by Western blot. The relationship between SYNJ2 and GRB2 was assessed by Co-immunoprecipitation (CO-IP) assay. SYNJ2 was highly expressed in GC tissues and cells. SYNJ2 overexpression promoted viability, migration, invasion, angiogenesis and GRB2 level, and inhibited apoptosis of GC cells, while shSYNJ2 exhibited opposite effects. GRB2 overexpression boosted yet shGRB2 suppressed cell migration, invasion and angiogenesis. Notably, SYNJ2 could interact with GRB2. GRB2 overexpression and shGRB2 reversed the effects of shSYNJ2 and overexpressed SYNJ2 on cell migration, invasion and angiogenesis and levels of metastasis-related proteins, respectively. In conclusion, SYNJ2 promotes GC cell metastasis and angiogenesis by up-regulating GRB2.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"78 ","pages":"Article 101990"},"PeriodicalIF":2.3,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-23DOI: 10.1016/j.mcp.2024.101992
Jinho Yang
Recently, the microbiome has been gaining significant attention in the healthcare sector as a next-generation factor. However, there remains a substantial gap in our understanding of the fundamental mechanisms of microbes, particularly regarding the effector microbial products exchanged between the microbiota and the host. Consequently, research on microbial extracellular vesicles (MEVs) has increased. MEVs, which are nano-sized, can circulate throughout the body and penetrate the bloodstream, carrying diverse information. Consequently, they are increasingly being utilized in medical applications. Additionally, AI technologies are being utilized in medicine. The combination of MEVs and AI technology is being explored for the development of algorithm-based in vitro diagnostics (IVD). Therefore, this study aims to review the integration of MEVs and AI technology as diagnostic tools for personalized medicine. This paper reviewed the MEV-based algorithms developed by a variety of human samples and AI technology. Additionally, most of MEV-based diagnostic models showed higher clinical performance. Several important factors are crucial for accurate diagnosis. First, optimizing sample types according to specific diseases is essential. Second, AI technology with higher diagnostic power yields more accurate results. Finally, incorporating additional markers can enhance diagnostic power. However, applying this tool in situ faces several limitations, including method standardization, sample size, and analysis techniques. In the future, we anticipate that research on MEVs will advance our understanding of their role in disease and establish the foundation for precision medicine strategies.
{"title":"Insight into the potential of algorithms using AI technology as in vitro diagnostics utilizing microbial extracellular vesicles","authors":"Jinho Yang","doi":"10.1016/j.mcp.2024.101992","DOIUrl":"10.1016/j.mcp.2024.101992","url":null,"abstract":"<div><div>Recently, the microbiome has been gaining significant attention in the healthcare sector as a next-generation factor. However, there remains a substantial gap in our understanding of the fundamental mechanisms of microbes, particularly regarding the effector microbial products exchanged between the microbiota and the host. Consequently, research on microbial extracellular vesicles (MEVs) has increased. MEVs, which are nano-sized, can circulate throughout the body and penetrate the bloodstream, carrying diverse information. Consequently, they are increasingly being utilized in medical applications. Additionally, AI technologies are being utilized in medicine. The combination of MEVs and AI technology is being explored for the development of algorithm-based in vitro diagnostics (IVD). Therefore, this study aims to review the integration of MEVs and AI technology as diagnostic tools for personalized medicine. This paper reviewed the MEV-based algorithms developed by a variety of human samples and AI technology. Additionally, most of MEV-based diagnostic models showed higher clinical performance. Several important factors are crucial for accurate diagnosis. First, optimizing sample types according to specific diseases is essential. Second, AI technology with higher diagnostic power yields more accurate results. Finally, incorporating additional markers can enhance diagnostic power. However, applying this tool <em>in situ</em> faces several limitations, including method standardization, sample size, and analysis techniques. In the future, we anticipate that research on MEVs will advance our understanding of their role in disease and establish the foundation for precision medicine strategies.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"78 ","pages":"Article 101992"},"PeriodicalIF":2.3,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Retinal photochemical damage (RPD) plays a significant role in the development of various ocular diseases, with Caspase-1 being a key contributor. This study investigates the protective effects of Caspase-1 gene-mediated pyroptosis against RPD.
Methods
Differentially expressed genes (DEGs) associated with RPD were identified through the analysis of two expression profiles from the GEO database. Correlation analysis was used to pinpoint pyroptosis-related genes (PRGs) linked to RPD. A Caspase-1 knockout 661 W cell line was generated via CRISPR-Cas9 gene editing, and single-cell colonies were screened and purified. Validation of knockout cells was performed through RT-qPCR, gene sequencing, and Western blot analysis. Comparative assays on cell proliferation, intracellular reactive oxygen species (ROS), and cytotoxicity were conducted between wild-type and Caspase-1 knockout cells under light exposure. Further RT-qPCR and Western blot experiments examined changes in the mRNA and protein levels of key pyroptosis pathway components.
Results
Significant alterations in Caspase-1 expression were observed among PRGs. Homozygous Caspase-1 knockout cell lines were confirmed through RT-qPCR, genomic PCR product sequencing, and Western blot analysis. Compared to wild-type 661 W cells, Caspase-1 knockout cells exhibited higher viability and proliferation rates after 24 h of light exposure, alongside reduced LDH release. The expression of downstream pyroptosis factors at both the mRNA and protein levels was markedly decreased in the knockout group.
Conclusion
CRISPR/Cas9-mediated Caspase-1 knockout enhanced the resistance of 661 W cells to photochemical damage, suggesting that Caspase-1 may serve as a potential therapeutic target for RPD-related diseases.
{"title":"Caspase-1 knockout disrupts pyroptosis and protects photoreceptor cells from photochemical damage","authors":"Xiaoping Yu , Jiayuan Peng , Qian Zhong , Ailin Wu , Xiaoming Deng , Yanfeng Zhu","doi":"10.1016/j.mcp.2024.101991","DOIUrl":"10.1016/j.mcp.2024.101991","url":null,"abstract":"<div><h3>Aim</h3><div>Retinal photochemical damage (RPD) plays a significant role in the development of various ocular diseases, with Caspase-1 being a key contributor. This study investigates the protective effects of Caspase-1 gene-mediated pyroptosis against RPD.</div></div><div><h3>Methods</h3><div>Differentially expressed genes (DEGs) associated with RPD were identified through the analysis of two expression profiles from the GEO database. Correlation analysis was used to pinpoint pyroptosis-related genes (PRGs) linked to RPD. A Caspase-1 knockout 661 W cell line was generated via CRISPR-Cas9 gene editing, and single-cell colonies were screened and purified. Validation of knockout cells was performed through RT-qPCR, gene sequencing, and Western blot analysis. Comparative assays on cell proliferation, intracellular reactive oxygen species (ROS), and cytotoxicity were conducted between wild-type and Caspase-1 knockout cells under light exposure. Further RT-qPCR and Western blot experiments examined changes in the mRNA and protein levels of key pyroptosis pathway components.</div></div><div><h3>Results</h3><div>Significant alterations in Caspase-1 expression were observed among PRGs. Homozygous Caspase-1 knockout cell lines were confirmed through RT-qPCR, genomic PCR product sequencing, and Western blot analysis. Compared to wild-type 661 W cells, Caspase-1 knockout cells exhibited higher viability and proliferation rates after 24 h of light exposure, alongside reduced LDH release. The expression of downstream pyroptosis factors at both the mRNA and protein levels was markedly decreased in the knockout group.</div></div><div><h3>Conclusion</h3><div>CRISPR/Cas9-mediated Caspase-1 knockout enhanced the resistance of 661 W cells to photochemical damage, suggesting that Caspase-1 may serve as a potential therapeutic target for RPD-related diseases.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"78 ","pages":"Article 101991"},"PeriodicalIF":2.3,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-07DOI: 10.1016/j.mcp.2024.101988
Jian Wu , Wenqiang Xu , Jingchi Li , Cheng Luo , Bo Chen , Luo Lin , Tianyu Huang , Tao Luo , Lin Yang , Jiexiang Yang
Background
Osteosarcoma (OS) is a common primary malignant tumor of bone, most commonly seen in children and adolescents, which has a low survival rate and is a serious threat to patients' lives. Honokiol (HKL) is the main active components of Magnolia officinalis, which have significant anti-tumor properties. The aim of this study was to observe the autophagic and migratory effects of HKL on MG63 cells and to investigate whether the mechanism of action was related to FTO and Smad6.
Methods
Firstly, we cultured MG63 cells in vitro and intervened with different concentrations of HKL to detect cell activity by CCK8, apoptosis by flow cytometry, cell migration ability by scratch assay, cell invasion ability by transwell assay and MMP2, P62, LC3 I/II, FTO and Smad6 protein expression by Western blot.
Results
HKL inhibited MG63 cells activity and that this effect was dose and time dependent. Although there was no significant effect on apoptosis and invasive ability, HKL could act through effects such as promoting cell autophagy and inhibiting migration. HKL increased the protein expression levels of FTO, Smad6, MMP2, LC3 I/II and P62, and this effect was reduced after silencing of Smad6.
Conclusions
HKL induced autophagy and inhibited cell migration in MG63 cells by increasing the expression of FTP and Smad6. It can be seen that HKL may be a promising drug for the treatment of OS.
{"title":"Honokiol inhibits human osteosarcoma MG63 cell migration by upregulating FTO and Smad6 to promote autophagy","authors":"Jian Wu , Wenqiang Xu , Jingchi Li , Cheng Luo , Bo Chen , Luo Lin , Tianyu Huang , Tao Luo , Lin Yang , Jiexiang Yang","doi":"10.1016/j.mcp.2024.101988","DOIUrl":"10.1016/j.mcp.2024.101988","url":null,"abstract":"<div><h3>Background</h3><div>Osteosarcoma (OS) is a common primary malignant tumor of bone, most commonly seen in children and adolescents, which has a low survival rate and is a serious threat to patients' lives. Honokiol (HKL) is the main active components of Magnolia officinalis, which have significant anti-tumor properties. The aim of this study was to observe the autophagic and migratory effects of HKL on MG63 cells and to investigate whether the mechanism of action was related to FTO and Smad6.</div></div><div><h3>Methods</h3><div>Firstly, we cultured MG63 cells in vitro and intervened with different concentrations of HKL to detect cell activity by CCK8, apoptosis by flow cytometry, cell migration ability by scratch assay, cell invasion ability by transwell assay and MMP2, P62, LC3 I/II, FTO and Smad6 protein expression by Western blot.</div></div><div><h3>Results</h3><div>HKL inhibited MG63 cells activity and that this effect was dose and time dependent. Although there was no significant effect on apoptosis and invasive ability, HKL could act through effects such as promoting cell autophagy and inhibiting migration. HKL increased the protein expression levels of FTO, Smad6, MMP2, LC3 I/II and P62, and this effect was reduced after silencing of Smad6.</div></div><div><h3>Conclusions</h3><div>HKL induced autophagy and inhibited cell migration in MG63 cells by increasing the expression of FTP and Smad6. It can be seen that HKL may be a promising drug for the treatment of OS.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"78 ","pages":"Article 101988"},"PeriodicalIF":2.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-31DOI: 10.1016/j.mcp.2024.101989
Hao Deng , Jinzhuo Ning , Yuan Ruan , Weimin Yu , Fan Cheng
TNFRSF11B contributes to tumorigenesis in many malignancies. Nevertheless, its function and underlying tumorigenic mechanism in bladder cancer (BC) has been rare.
The clinical significance and relevant signaling pathway of TNFRSF11B in BC were assessed using bioinformatic analysis. The determination of TNFRSF11B expression was conducted in bladder tissues and BC cells. BC cells were subjected to functional experiments to evaluate their ability to proliferate, migrate, and invade. Cell apoptosis experiments were conducted. The protein levels of markers associated with epithelial-mesenchymal transition (EMT) and molecules linked to the PI3K/AKT pathway were assessed. To evaluate the effect of the PI3K/AKT pathway on TNFRSF11B, LY294002, a PI3K/AKT pathway inhibitor, was utilized. TNFRSF11B exhibited significant upregulation in both BC tissues and various cell lines. Inhibited TNFRSF11B expression impeded the growth, movement, infiltration of BC cells. Conversely, the ultimate outcome varied when TNFRSF11B was overexpressed. In vivo assay further confirmed the above results. Furthermore, TNFRSF11B promoted malignant traits by controlling the PI3K/AKT pathway. In BC, TNFRSF11B exhibits elevated expression levels and has a substantial tumor-promoting role in BC via the PI3K/AKT pathway. Importantly, TNFRSF11B may represent a valuable prognostic tumor marker for BC treatment.
TNFRSF11B 在许多恶性肿瘤中都有助于肿瘤的发生。然而，它在膀胱癌（BC）中的功能及其潜在的致瘤机制却很少见。本研究利用生物信息学分析评估了TNFRSF11B在膀胱癌中的临床意义和相关信号通路。在膀胱组织和BC细胞中测定了TNFRSF11B的表达。对 BC 细胞进行功能实验，评估其增殖、迁移和侵袭能力。还进行了细胞凋亡实验。评估了与上皮-间质转化（EMT）相关的标记物和与 PI3K/AKT 通路相关的分子的蛋白水平。为了评估 PI3K/AKT 通路对 TNFRSF11B 的影响，使用了 PI3K/AKT 通路抑制剂 LY294002。TNFRSF11B在BC组织和各种细胞系中均表现出明显的上调。抑制 TNFRSF11B 的表达会阻碍 BC 细胞的生长、移动和浸润。相反，当TNFRSF11B表达过高时，最终的结果也不尽相同。体内试验进一步证实了上述结果。此外，TNFRSF11B通过控制PI3K/AKT通路促进恶性特征。在BC中，TNFRSF11B的表达水平升高，并通过PI3K/AKT通路对BC的肿瘤有实质性的促进作用。重要的是，TNFRSF11B可能是一种有价值的预后肿瘤标志物，可用于BC的治疗。
{"title":"TNFRSF11B promotes the progression of bladder cancer through PI3K/AKT signaling pathway","authors":"Hao Deng , Jinzhuo Ning , Yuan Ruan , Weimin Yu , Fan Cheng","doi":"10.1016/j.mcp.2024.101989","DOIUrl":"10.1016/j.mcp.2024.101989","url":null,"abstract":"<div><div>TNFRSF11B contributes to tumorigenesis in many malignancies. Nevertheless, its function and underlying tumorigenic mechanism in bladder cancer (BC) has been rare.</div><div>The clinical significance and relevant signaling pathway of TNFRSF11B in BC were assessed using bioinformatic analysis. The determination of TNFRSF11B expression was conducted in bladder tissues and BC cells. BC cells were subjected to functional experiments to evaluate their ability to proliferate, migrate, and invade. Cell apoptosis experiments were conducted. The protein levels of markers associated with epithelial-mesenchymal transition (EMT) and molecules linked to the PI3K/AKT pathway were assessed. To evaluate the effect of the PI3K/AKT pathway on TNFRSF11B, LY294002, a PI3K/AKT pathway inhibitor, was utilized. TNFRSF11B exhibited significant upregulation in both BC tissues and various cell lines. Inhibited TNFRSF11B expression impeded the growth, movement, infiltration of BC cells. Conversely, the ultimate outcome varied when TNFRSF11B was overexpressed. In vivo assay further confirmed the above results. Furthermore, TNFRSF11B promoted malignant traits by controlling the PI3K/AKT pathway. In BC, TNFRSF11B exhibits elevated expression levels and has a substantial tumor-promoting role in BC via the PI3K/AKT pathway. Importantly, TNFRSF11B may represent a valuable prognostic tumor marker for BC treatment.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"78 ","pages":"Article 101989"},"PeriodicalIF":2.3,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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