Pub Date : 2025-02-01DOI: 10.1016/j.mcp.2025.102010
Hua Ji , Sicheng Liu , Libo Yang , Yunhua Wu , Huanqing Zhang , Xueqing Liu , Linhai Li , Lihua Li
Gastric cancer (GC), among the most prevalent malignant tumors globally, demonstrates a rapid metastasis rate leading to high mortality. While microRNAs (miRNAs) have been recognized as critical regulators of tumor progression, the specific role of miR-28–3p in GC remains unclear. In this study, we demonstrate that miR-28–3p acts as a tumor suppressor by inhibiting GC cell proliferation and EMT-driven migration in vitro, as well as tumor growth and metastasis in vivo. Mechanistically, miR-28–3p directly targets ADP ribosylation factor 6 (ARF6), a small GTPase identified as an oncogene in GC. We reveal that ARF6 is significantly upregulated in GC and activates the GLI1/2-dependent Hedgehog signaling pathway, promoting tumor growth and EMT. Notably, ARF6 knockdown mitigates the pro-tumor effects caused by miR-28–3p deficiency, while combined ARF6 inhibition and Hedgehog pathway suppression exhibit synergistic anti-tumor effects. This study establishes the miR-28-3p-ARF6-Hedgehog signaling axis as a critical regulatory pathway in GC progression. Our findings provide novel insights into GC pathogenesis and highlight the therapeutic potential of targeting this axis for innovative treatment strategies.
{"title":"miR-28–3p suppresses gastric cancer growth and EMT-driven metastasis by targeting the ARF6/Hedgehog axis","authors":"Hua Ji , Sicheng Liu , Libo Yang , Yunhua Wu , Huanqing Zhang , Xueqing Liu , Linhai Li , Lihua Li","doi":"10.1016/j.mcp.2025.102010","DOIUrl":"10.1016/j.mcp.2025.102010","url":null,"abstract":"<div><div>Gastric cancer (GC), among the most prevalent malignant tumors globally, demonstrates a rapid metastasis rate leading to high mortality. While microRNAs (miRNAs) have been recognized as critical regulators of tumor progression, the specific role of miR-28–3p in GC remains unclear. In this study, we demonstrate that miR-28–3p acts as a tumor suppressor by inhibiting GC cell proliferation and EMT-driven migration in vitro, as well as tumor growth and metastasis in vivo. Mechanistically, miR-28–3p directly targets ADP ribosylation factor 6 (ARF6), a small GTPase identified as an oncogene in GC. We reveal that ARF6 is significantly upregulated in GC and activates the GLI1/2-dependent Hedgehog signaling pathway, promoting tumor growth and EMT. Notably, ARF6 knockdown mitigates the pro-tumor effects caused by miR-28–3p deficiency, while combined ARF6 inhibition and Hedgehog pathway suppression exhibit synergistic anti-tumor effects. This study establishes the miR-28-3p-ARF6-Hedgehog signaling axis as a critical regulatory pathway in GC progression. Our findings provide novel insights into GC pathogenesis and highlight the therapeutic potential of targeting this axis for innovative treatment strategies.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"79 ","pages":"Article 102010"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957845","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 : 2025-02-01DOI: 10.1016/j.mcp.2025.102016
Xia Yin , Chunlei Zhang
Background
Early screening is critical for the prevention of ischemic stroke. miR-574–5p was considered a promising biomarker for ischemic stroke but lacks direct confirmation. This study evaluated miR-574–5p in discriminating ischemic stroke and predicting the severity and prognosis of patients, aiming to provide novel insights into the clinical prevention of ischemic stroke.
Methods
The clinical significance of miR-574–5p was evaluated in 103 ischemic stroke patients with 87 healthy individuals as control. The potential of serum miR-574–5p in the diagnosis and prognosis of ischemic stroke was assessed by ROC and logistic regression analyses. In vitro, oxygen-glucose deprivation (OGD)-induced microglia was established. The regulation of inflammation, oxidative stress, and proliferation of microglia by miR-574–5p were assessed by cell transfection. The downstream targets of miR-574–5p were predicted from public databases, and the targeting relationship was evaluated by luciferase reporter assay.
Results
Reducing serum miR-574–5p was observed in ischemic stroke patients relative to healthy individuals, which discriminated ischemic stroke patients. Serum miR-574–5p was negatively correlated with the NIHSS score of ischemic stroke patients and was identified as a risk factor for patients’ adverse prognosis. In OGD-induced microglia, overexpressing miR-574–5p could alleviate OGD-induced inflammation and oxidative stress and promote cell growth. Among predicted targets, ATP2B2 was upregulated in ischemic stroke and showed a negative correlation with miR-574–5p. miR-574–5p negatively regulated ATP2B2 in OGD-induced microglia, and the overexpression of ATP2B2 reversed the protective effect of miR-574–5p.
Conclusion
miR-574–5p acted as a biomarker for ischemic stroke and mediated neuroinflammation via targeting ATP2B2.
{"title":"Circulating miR-574–5p shows diagnostic and prognostic significance and regulates oxygen-glucose deprivation (OGD)-induced inflammatory activation of microglia by targeting ATP2B2","authors":"Xia Yin , Chunlei Zhang","doi":"10.1016/j.mcp.2025.102016","DOIUrl":"10.1016/j.mcp.2025.102016","url":null,"abstract":"<div><h3>Background</h3><div>Early screening is critical for the prevention of ischemic stroke. miR-574–5p was considered a promising biomarker for ischemic stroke but lacks direct confirmation. This study evaluated miR-574–5p in discriminating ischemic stroke and predicting the severity and prognosis of patients, aiming to provide novel insights into the clinical prevention of ischemic stroke.</div></div><div><h3>Methods</h3><div>The clinical significance of miR-574–5p was evaluated in 103 ischemic stroke patients with 87 healthy individuals as control. The potential of serum miR-574–5p in the diagnosis and prognosis of ischemic stroke was assessed by ROC and logistic regression analyses. In vitro, oxygen-glucose deprivation (OGD)-induced microglia was established. The regulation of inflammation, oxidative stress, and proliferation of microglia by miR-574–5p were assessed by cell transfection. The downstream targets of miR-574–5p were predicted from public databases, and the targeting relationship was evaluated by luciferase reporter assay.</div></div><div><h3>Results</h3><div>Reducing serum miR-574–5p was observed in ischemic stroke patients relative to healthy individuals, which discriminated ischemic stroke patients. Serum miR-574–5p was negatively correlated with the NIHSS score of ischemic stroke patients and was identified as a risk factor for patients’ adverse prognosis. In OGD-induced microglia, overexpressing miR-574–5p could alleviate OGD-induced inflammation and oxidative stress and promote cell growth. Among predicted targets, ATP2B2 was upregulated in ischemic stroke and showed a negative correlation with miR-574–5p. miR-574–5p negatively regulated ATP2B2 in OGD-induced microglia, and the overexpression of ATP2B2 reversed the protective effect of miR-574–5p.</div></div><div><h3>Conclusion</h3><div>miR-574–5p acted as a biomarker for ischemic stroke and mediated neuroinflammation via targeting ATP2B2.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"79 ","pages":"Article 102016"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069239","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.2024.101994
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}
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 : 2024-12-01DOI: 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}
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 : 2024-11-25DOI: 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}
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