Pub Date : 2025-05-13DOI: 10.1016/j.mcp.2025.102031
Xin Song , Sihao Chen , Junning Cheng , Haiyu Li , Ruixin Wu , Min Yan , Min Wang , Jie Li , Aishun Jin , Wang Wang
Purpose
Osteosarcoma (OS) exhibits limited immune cell infiltration that directly contributes to poor prognosis. This study sought to screen and identify pivotal biomarkers of OS immune infiltration and early diagnosis of OS.
Methods
The immune cell infiltration profiles with transcriptome sequencing data from 88 OS samples were explored with CIBERSORT algorithm. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein-protein interaction (PPI) network analyses were applied to identify hub genes, with the expressions confirmed by dual immunofluorescence in 50 OS samples. The new biomarker gene HTRA1 were examined by immunohistochemistry and validated by the Immune score and immune gene expression profile analyses. The impact of HTRA1 on OS prognosis was verified by Least absolute shrinkage and selection operator (LASSO) regression analysis. The biological effect of HTRA1 was characterized in MG63 cells.
Result
CD8+ T cells, activated memory CD4+ T cells and plasma cells were positively correlated with the prognosis of OS. Hub genes CCL5, CXCL9, CXCL13, and HTRA1, exhibited positive correlation with the infiltration of both CD8+ T cells and CD4+ T cells. HTRA1 expression was reduced in osteosarcoma tissues, which was positively correlated with immune scores and the expressions of immune-related genes. High levels of HTRA1 were associated with favorable OS prognosis, and could negatively impacted MG63 malignant characteristics.
Conclusion
CCL5, CXCL9, CXCL13, and HTRA1 were OS hub genes positively correlate with CD8+ T cell and CD4+ T cell infiltrations. HTRA1 can serve as an underlying biomarker for the prognosis and immunotherapy of OS.
{"title":"Screening and identification Hub genes associated with immune cell infiltration and critical biomarkers in osteosarcoma","authors":"Xin Song , Sihao Chen , Junning Cheng , Haiyu Li , Ruixin Wu , Min Yan , Min Wang , Jie Li , Aishun Jin , Wang Wang","doi":"10.1016/j.mcp.2025.102031","DOIUrl":"10.1016/j.mcp.2025.102031","url":null,"abstract":"<div><h3>Purpose</h3><div>Osteosarcoma (OS) exhibits limited immune cell infiltration that directly contributes to poor prognosis. This study sought to screen and identify pivotal biomarkers of OS immune infiltration and early diagnosis of OS.</div></div><div><h3>Methods</h3><div>The immune cell infiltration profiles with transcriptome sequencing data from 88 OS samples were explored with CIBERSORT algorithm. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein-protein interaction (PPI) network analyses were applied to identify hub genes, with the expressions confirmed by dual immunofluorescence in 50 OS samples. The new biomarker gene HTRA1 were examined by immunohistochemistry and validated by the Immune score and immune gene expression profile analyses. The impact of HTRA1 on OS prognosis was verified by Least absolute shrinkage and selection operator (LASSO) regression analysis. The biological effect of HTRA1 was characterized in MG63 cells.</div></div><div><h3>Result</h3><div>CD8<sup>+</sup> T cells, activated memory CD4<sup>+</sup> T cells and plasma cells were positively correlated with the prognosis of OS. Hub genes <em>CCL5</em>, <em>CXCL9</em>, <em>CXCL13</em>, and <em>HTRA1</em>, exhibited positive correlation with the infiltration of both CD8<sup>+</sup> T cells and CD4<sup>+</sup> T cells. HTRA1 expression was reduced in osteosarcoma tissues, which was positively correlated with immune scores and the expressions of immune-related genes. High levels of HTRA1 were associated with favorable OS prognosis, and could negatively impacted MG63 malignant characteristics.</div></div><div><h3>Conclusion</h3><div><em>CCL5</em>, <em>CXCL9</em>, <em>CXCL13,</em> and <em>HTRA1</em> were OS hub genes positively correlate with CD8<sup>+</sup> T cell and CD4<sup>+</sup> T cell infiltrations. HTRA1 can serve as an underlying biomarker for the prognosis and immunotherapy of OS.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"82 ","pages":"Article 102031"},"PeriodicalIF":2.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081636","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 : 2025-04-28DOI: 10.1016/j.mcp.2025.102030
Xiaohong Liu , Yelin Zhao , Li Zhang , Junting Wang , Liaoxin Luo , Shihui Zhang , Qin Zhu , Yuchen Shi , Chenyu Yuan , Qifeng Xiao , Mengran Xiong , Yuanyuan Duan , Hebing Chen , Hongjuan Yao , Lin Cai , Jianwei Zhang , Guangxi Li , Liang Li
Purpose
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and fatal malignancy, although gemcitabine is administered as a single or combined therapeutic agent. Our previous study demonstrated that ANP32E overexpression promoted PDAC cell proliferation. However, whether it affects treatment outcome and clinical prognosis is still unclear. In the present study, we aimed to determine whether ANP32E is negatively associated with the treatment outcome of gemcitabine.
Methods
We collected clinical characteristics and treatment information from a total of 75 PDAC patients to assess the association of ANP32E expression via immunohistochemical (IHC) staining with overall survival (OS) in patients who were or were not treated with gemcitabine-based chemotherapy, followed by a clinical replication study with transcriptomic data from the TCGA database and functional validation experiments involving the knockdown of ANP32E in the Hup-T3 and SU86.86 human pancreatic cancer cell lines.
Results
We demonstrated the interference effect of ANP32E on gemcitabine efficacy and patient prognosis in PDAC patients by using our own clinical samples or publicly available TCGA datasets. Downregulation of ANP32E significantly sensitized Hup-T3 and SU86.86 cells to gemcitabine, which was consistent with the results of the above association studies.
Conclusion
Our findings suggest that ANP32E might serve as a negative biomarker for poor prognosis and a predictive indicator for poor gemcitabine efficacy. These findings suggest that ANP32E might be a potential therapeutic target to help develop effective drugs to overcome gemcitabine resistance and reduce the risk for relapse or metastasis in patients with PDAC.
{"title":"ANP32E expression in pancreatic cancer is associated with impaired gemcitabine efficacy and poor patient prognosis","authors":"Xiaohong Liu , Yelin Zhao , Li Zhang , Junting Wang , Liaoxin Luo , Shihui Zhang , Qin Zhu , Yuchen Shi , Chenyu Yuan , Qifeng Xiao , Mengran Xiong , Yuanyuan Duan , Hebing Chen , Hongjuan Yao , Lin Cai , Jianwei Zhang , Guangxi Li , Liang Li","doi":"10.1016/j.mcp.2025.102030","DOIUrl":"10.1016/j.mcp.2025.102030","url":null,"abstract":"<div><h3>Purpose</h3><div>Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and fatal malignancy, although gemcitabine is administered as a single or combined therapeutic agent. Our previous study demonstrated that ANP32E overexpression promoted PDAC cell proliferation. However, whether it affects treatment outcome and clinical prognosis is still unclear. In the present study, we aimed to determine whether ANP32E is negatively associated with the treatment outcome of gemcitabine.</div></div><div><h3>Methods</h3><div>We collected clinical characteristics and treatment information from a total of 75 PDAC patients to assess the association of ANP32E expression via immunohistochemical (IHC) staining with overall survival (OS) in patients who were or were not treated with gemcitabine-based chemotherapy, followed by a clinical replication study with transcriptomic data from the TCGA database and functional validation experiments involving the knockdown of ANP32E in the Hup-T3 and SU86.86 human pancreatic cancer cell lines.</div></div><div><h3>Results</h3><div>We demonstrated the interference effect of ANP32E on gemcitabine efficacy and patient prognosis in PDAC patients by using our own clinical samples or publicly available TCGA datasets. Downregulation of ANP32E significantly sensitized Hup-T3 and SU86.86 cells to gemcitabine, which was consistent with the results of the above association studies.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that ANP32E might serve as a negative biomarker for poor prognosis and a predictive indicator for poor gemcitabine efficacy. These findings suggest that ANP32E might be a potential therapeutic target to help develop effective drugs to overcome gemcitabine resistance and reduce the risk for relapse or metastasis in patients with PDAC.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"82 ","pages":"Article 102030"},"PeriodicalIF":2.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902338","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}
CD44 is a promising target in the prognosis and treatment of non-small cell lung cancer (NSCLC). The study deals with systematic review and meta-analysis to determine the association between CD44 overexpression and survival and clinicopathological characteristics in NSCLC patients.
Methods
We used the databases Google Scholar, Web of Science, PubMed, Scopus, EMBASE, and Cochrane to conduct a systematic search of English-language literature published up to September 2023. The eligible studies were retrieved on CD44 expression, clinicopathological characteristics in NSCLC patients, and reported survival rates. The Cochran's and Higgins I2 tests were used to measure heterogeneity across the included studies. P < 0.05 was considered statistically significant in all cases. The sources of heterogeneity across the included studies were identified using subgroup analysis on histology (SCC, ADC, and LCC), tumor differentiation (well, moderate, and poor), TMN stage (I/II/III/IV), OS, and lymph node metastasis (negative and positive). All statistical analyses were carried out using meta-analysis (CMA) software.
Results
The final analysis for prognostic significance and clinicopathological features on 3681 participants from 25 eligible studies. The pooled event rate of overexpression CD44 for overall survival in NSCLC was 38 % and was related to SCC with 76.6 %. Furthermore, subgroup analysis revealed a link between CD44 overexpression and moderate tumor differentiation (41.8 %). There was a substantial difference in CD44 overexpression in males, with 69.3 % (95 % CI: 64.3–73.9 %, I2 = 88.25 %) versus 31.5 % (95 % CI: 26.7–36.8 %, I2 = 92.15 %) in females. However, no significant relationship was observed between CD44 overexpression and TMN stages/lymph node metastasis.
Conclusion
The meta-analysis demonstrated that CD44 is an effective prognostic factor for NSCLC. Overexpression of CD44 has been linked to moderate tumor differentiation, SCC tumor histology, and a worse survival rate. However, no substantial relationship was found between CD44 and metastasis or TMN stages. Large-scale prospective research is required to validate CD44's clinical value as an unbiased prognostic indicator.
{"title":"The clinicopathologic and prognostic value of CD44 expression in patients with non-small cell lung cancer: A systematic review and meta-analysis","authors":"Elmira Alaei , Najma Farahani , Sima Orouei , Mina Alimohammadi , Salman Daneshi , Tahoora Mousavi , Behnaz Mahmoodieh , Afshin Taheriazam , Payman Rahimzadeh , Mehrdad Hashemi","doi":"10.1016/j.mcp.2025.102028","DOIUrl":"10.1016/j.mcp.2025.102028","url":null,"abstract":"<div><h3>Background</h3><div>CD44 is a promising target in the prognosis and treatment of non-small cell lung cancer (NSCLC). The study deals with systematic review and meta-analysis to determine the association between CD44 overexpression and survival and clinicopathological characteristics in NSCLC patients.</div></div><div><h3>Methods</h3><div>We used the databases Google Scholar, Web of Science, PubMed, Scopus, EMBASE, and Cochrane to conduct a systematic search of English-language literature published up to September 2023. The eligible studies were retrieved on CD44 expression, clinicopathological characteristics in NSCLC patients, and reported survival rates. The Cochran's and Higgins I<sup>2</sup> tests were used to measure heterogeneity across the included studies. P < 0.05 was considered statistically significant in all cases. The sources of heterogeneity across the included studies were identified using subgroup analysis on histology (SCC, ADC, and LCC), tumor differentiation (well, moderate, and poor), TMN stage (I/II/III/IV), OS, and lymph node metastasis (negative and positive). All statistical analyses were carried out using meta-analysis (CMA) software.</div></div><div><h3>Results</h3><div>The final analysis for prognostic significance and clinicopathological features on 3681 participants from 25 eligible studies. The pooled event rate of overexpression CD44 for overall survival in NSCLC was 38 % and was related to SCC with 76.6 %. Furthermore, subgroup analysis revealed a link between CD44 overexpression and moderate tumor differentiation (41.8 %). There was a substantial difference in CD44 overexpression in males, with 69.3 % (95 % CI: 64.3–73.9 %, I<sup>2</sup> = 88.25 %) versus 31.5 % (95 % CI: 26.7–36.8 %, I<sup>2</sup> = 92.15 %) in females. However, no significant relationship was observed between CD44 overexpression and TMN stages/lymph node metastasis.</div></div><div><h3>Conclusion</h3><div>The meta-analysis demonstrated that CD44 is an effective prognostic factor for NSCLC. Overexpression of CD44 has been linked to moderate tumor differentiation, SCC tumor histology, and a worse survival rate. However, no substantial relationship was found between CD44 and metastasis or TMN stages. Large-scale prospective research is required to validate CD44's clinical value as an unbiased prognostic indicator.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"81 ","pages":"Article 102028"},"PeriodicalIF":2.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143714457","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 : 2025-03-14DOI: 10.1016/j.mcp.2025.102027
Dominik Kodada , Dominik Hadžega , Patrik Krumpolec , Nikola Janoštiaková , Gabriela Bľandová , Pavol Janega , Zuzana Ballová , Erik Dosedla , Gabriel Minárik , Vanda Repiská
Endometrial cancer is a significant public health concern with rising incidence rates globally. Understanding the molecular mechanisms underlying this disease is crucial for developing effective therapeutic strategies. Our study aimed to characterize transcriptional changes in endometrial cancer tissues compared to adjusted healthy tissue. Using RNA sequencing, we identified 2483 differentially expressed genes (DEGs), including protein-coding genes, long non-coding RNAs (lncRNAs), and microRNAs (miRNAs). Notably, several known cancer-related genes were differentially expressed, such as MYC, AKT3, CCND1, and CDKN2A. Pathway analysis revealed significant alterations in cell cycle regulation, several signaling pathways, and metabolic processes. These findings provide valuable insights into the molecular pathways dysregulated in endometrial cancer. Our results may contribute to the development of novel therapeutic targets and biomarkers for this disease.
{"title":"Differential gene expression in uterine endometrioid cancer cells and adjusted normal tissue","authors":"Dominik Kodada , Dominik Hadžega , Patrik Krumpolec , Nikola Janoštiaková , Gabriela Bľandová , Pavol Janega , Zuzana Ballová , Erik Dosedla , Gabriel Minárik , Vanda Repiská","doi":"10.1016/j.mcp.2025.102027","DOIUrl":"10.1016/j.mcp.2025.102027","url":null,"abstract":"<div><div>Endometrial cancer is a significant public health concern with rising incidence rates globally. Understanding the molecular mechanisms underlying this disease is crucial for developing effective therapeutic strategies. Our study aimed to characterize transcriptional changes in endometrial cancer tissues compared to adjusted healthy tissue. Using RNA sequencing, we identified 2483 differentially expressed genes (DEGs), including protein-coding genes, long non-coding RNAs (lncRNAs), and microRNAs (miRNAs). Notably, several known cancer-related genes were differentially expressed, such as <em>MYC</em>, <em>AKT3</em>, <em>CCND1</em>, and <em>CDKN2A</em>. Pathway analysis revealed significant alterations in cell cycle regulation, several signaling pathways, and metabolic processes. These findings provide valuable insights into the molecular pathways dysregulated in endometrial cancer. Our results may contribute to the development of novel therapeutic targets and biomarkers for this disease.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"81 ","pages":"Article 102027"},"PeriodicalIF":2.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639840","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 : 2025-03-14DOI: 10.1016/j.mcp.2025.102026
Deepti Kailash Nabariya , Lisa Maria Knüpfer , Patrick Hartwich , Manuela S. Killian , Florian Centler , Sybille Krauß
Huntington's disease (HD) arises from the abnormal expansion of a CAG repeat in the HTT gene. The mutant CAG repeat triggers aberrant RNA-protein interactions and translates into toxic aggregate-prone polyglutamine protein. These aberrant RNA-protein ineractions also seed the formation of cytoplasmic liquid-like granules, such as stress granules. Emerging evidence demonstrates that granules formed via liquid-liquid phase separation can mature into gel-like inclusions that persist within the cell and may act as precursor to aggregates that occur in patients' tissue. Thus, deregulation of RNA granules is an important component of neurodegeneration. Interestingly, both the formation of intracellular membrane-less organelles like stress granules and the secretion of small extracellular vesicles (sEVs) increase upon stress and under disease conditions. sEVs are lipid membrane-bound particles that are secreted from all cell types and may participate in the spreading of misfolded proteins and aberrant RNA-protein complexes across the central nervous system in neurodegenerative diseases like HD. In this study, we performed a comparative transcriptomic analysis of sEVs and RNA granules in an HD model. RNA granules and sEVs were isolated from an inducible HD cell model. Both sEVs and RNA granules were isolated from induced (HD) and non-induced (control) cells and analyzed by RNA sequencing. Our comparative analysis between the transcriptomics data of HD RNA granules and sEVs showed that: (I) intracellular RNA granules and extracellular RNA vesicles share content, (II) several non-coding RNAs translocate to RNA granules, and (III) the composition of RNA granules and sEVs is affected in HD cells. Our data showing common transcripts in intracellular RNA granules and extracellular sEVs suggest that formation of RNA granules and sEV loading may be related. Moreover, we found a high abundance of lncRNAs in both control and HD samples, with several transcripts under REST regulation, highlighting their potential role in HD pathogenesis and selective incorporation into sEVs. The transcriptome cargo of RNA granules or sEVs may serve as a source for diagnostic strategies. For example, disease-specific RNA-signatures of sEVs can serve as biomarker of central nervous system diseases. Therefore, we compared our dataset to transcriptomic data from HD patient sEVs in blood. However, our data suggest that the cell-type specific signature of sEV-secreted RNAs as well as their high variability may make it difficult to detect these biomarkers in blood.
{"title":"Transcriptomic analysis of intracellular RNA granules and small extracellular vesicles: Unmasking their overlap in a cell model of Huntington's disease","authors":"Deepti Kailash Nabariya , Lisa Maria Knüpfer , Patrick Hartwich , Manuela S. Killian , Florian Centler , Sybille Krauß","doi":"10.1016/j.mcp.2025.102026","DOIUrl":"10.1016/j.mcp.2025.102026","url":null,"abstract":"<div><div>Huntington's disease (HD) arises from the abnormal expansion of a CAG repeat in the <em>HTT</em> gene. The mutant CAG repeat triggers aberrant RNA-protein interactions and translates into toxic aggregate-prone polyglutamine protein. These aberrant RNA-protein ineractions also seed the formation of cytoplasmic liquid-like granules, such as stress granules. Emerging evidence demonstrates that granules formed via liquid-liquid phase separation can mature into gel-like inclusions that persist within the cell and may act as precursor to aggregates that occur in patients' tissue. Thus, deregulation of RNA granules is an important component of neurodegeneration. Interestingly, both the formation of intracellular membrane-less organelles like stress granules and the secretion of small extracellular vesicles (sEVs) increase upon stress and under disease conditions. sEVs are lipid membrane-bound particles that are secreted from all cell types and may participate in the spreading of misfolded proteins and aberrant RNA-protein complexes across the central nervous system in neurodegenerative diseases like HD. In this study, we performed a comparative transcriptomic analysis of sEVs and RNA granules in an HD model. RNA granules and sEVs were isolated from an inducible HD cell model. Both sEVs and RNA granules were isolated from induced (HD) and non-induced (control) cells and analyzed by RNA sequencing. Our comparative analysis between the transcriptomics data of HD RNA granules and sEVs showed that: (I) intracellular RNA granules and extracellular RNA vesicles share content, (II) several non-coding RNAs translocate to RNA granules, and (III) the composition of RNA granules and sEVs is affected in HD cells. Our data showing common transcripts in intracellular RNA granules and extracellular sEVs suggest that formation of RNA granules and sEV loading may be related. Moreover, we found a high abundance of lncRNAs in both control and HD samples, with several transcripts under REST regulation, highlighting their potential role in HD pathogenesis and selective incorporation into sEVs. The transcriptome cargo of RNA granules or sEVs may serve as a source for diagnostic strategies. For example, disease-specific RNA-signatures of sEVs can serve as biomarker of central nervous system diseases. Therefore, we compared our dataset to transcriptomic data from HD patient sEVs in blood. However, our data suggest that the cell-type specific signature of sEV-secreted RNAs as well as their high variability may make it difficult to detect these biomarkers in blood.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"81 ","pages":"Article 102026"},"PeriodicalIF":2.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639767","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 : 2025-03-11DOI: 10.1016/j.mcp.2025.102024
Xiaolin Zi , Jinpeng Ma , Xiaoxia Li , Honglei Wang , Yuchen Bao , Tao Deng , Xueli Yuan
Although great advances have been reached in the diagnosis, treatment and prognosis of kidney renal clear cell carcinoma (KIRC), the advancement of therapeutic strategies for KIRC in clinical practices have been seriously limited due to its unknown molecular mechanisms. To resolve this issue, through analyzing the datasets from the online UCSC database, a novel BUB1 gene was found to be elevated in the cancerous tissues compared to their normal tissues of KIRC, and and KIRC patients with high-expressed BUB1 tended to have a worse prognosis. The subsequent experiments validated that BUB1 protein was located in both nucleus and cytoplasm of KIRC cells, and the expression levels of BUB1 gene were significantly elevated in KIRC tissues and cells, in contrast to their normal counterparts. Loss-of-function experiments verified that knockdown of BUB1 suppressed cell proliferation, mobility, epithelial-mesenchymal transition (EMT) and tumor growth, whereas induced apoptotic cell death in the KIRC cells in vitro and in vivo. In addition, bioinformatics analysis predicted that the differentially-expressed genes (DEGs) in the BUB1-deficient cohorts were enriched in the cell division-related PI3K/Akt signal pathway, and we evidenced that silencing of BUB1 was capable of inactivating the downstream PI3K/Akt signal pathway. Of note, deficiency of BUB1-induced suppressing effects on the malignant phenotypes in KIRC cells were all reversed by co-treating cells with PI3K/Akt pathway activator 740Y-P. Furthermore, it was found that the expression status of BUB1 gene were related with epigenetic modifications, immune infiltration and immunotherapy responses in KIRC. Collectively, silencing of BUB1 inhibited the progression of KIRC through inactivating the downstream PI3K/Akt signal pathway, and BUB1 gene could be potentially used as biomarkers for the diagnosis and treatment of KIRC in clinic.
{"title":"BUB1-deficiency suppresses kidney renal clear cell carcinoma progression via the PI3K/Akt pathway: A bioinformatics-oriented validating study","authors":"Xiaolin Zi , Jinpeng Ma , Xiaoxia Li , Honglei Wang , Yuchen Bao , Tao Deng , Xueli Yuan","doi":"10.1016/j.mcp.2025.102024","DOIUrl":"10.1016/j.mcp.2025.102024","url":null,"abstract":"<div><div>Although great advances have been reached in the diagnosis, treatment and prognosis of kidney renal clear cell carcinoma (KIRC), the advancement of therapeutic strategies for KIRC in clinical practices have been seriously limited due to its unknown molecular mechanisms. To resolve this issue, through analyzing the datasets from the online UCSC database, a novel BUB1 gene was found to be elevated in the cancerous tissues compared to their normal tissues of KIRC, and and KIRC patients with high-expressed BUB1 tended to have a worse prognosis. The subsequent experiments validated that BUB1 protein was located in both nucleus and cytoplasm of KIRC cells, and the expression levels of BUB1 gene were significantly elevated in KIRC tissues and cells, in contrast to their normal counterparts. Loss-of-function experiments verified that knockdown of BUB1 suppressed cell proliferation, mobility, epithelial-mesenchymal transition (EMT) and tumor growth, whereas induced apoptotic cell death in the KIRC cells <em>in vitro</em> and <em>in vivo</em>. In addition, bioinformatics analysis predicted that the differentially-expressed genes (DEGs) in the BUB1-deficient cohorts were enriched in the cell division-related PI3K/Akt signal pathway, and we evidenced that silencing of BUB1 was capable of inactivating the downstream PI3K/Akt signal pathway. Of note, deficiency of BUB1-induced suppressing effects on the malignant phenotypes in KIRC cells were all reversed by co-treating cells with PI3K/Akt pathway activator 740Y-P. Furthermore, it was found that the expression status of BUB1 gene were related with epigenetic modifications, immune infiltration and immunotherapy responses in KIRC. Collectively, silencing of BUB1 inhibited the progression of KIRC through inactivating the downstream PI3K/Akt signal pathway, and BUB1 gene could be potentially used as biomarkers for the diagnosis and treatment of KIRC in clinic.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"81 ","pages":"Article 102024"},"PeriodicalIF":2.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626545","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 : 2025-03-07DOI: 10.1016/j.mcp.2025.102023
Qian Xu, Ailing Peng, Liyun Zhao, Li Wang
Background
To investigate the diagnostic value and mechanism of action of circular RNA (circ_) circ_0001853 and microRNA (miR) miR-34c-5p in patients with endometritis.
Methods
189 patients with endometritis and 176 healthy individuals were included in this study. Venous blood serum was collected from the study subjects and stored temporarily at −80 °C. Real-time quantitative chain polymerase reaction (RT-qPCR) was used to detect circ_0001853 and miR-34c-5p expression, and receiver operating characteristic (ROC) curves assessed the diagnostic value of both in predicting endometritis. Cell counting kit (CCK8) observed cell proliferation, flow cytometry recorded apoptosis, enzyme linked immunosorbent assay (ELISA) monitored inflammatory factor expression, and dual luciferase reporter assay and RNA immunoprecipitation (RIP) verified the relationship between circ_0001853 and miR-34c-5p targeting interactions.
Results
High levels of circ_0001853 and low levels of miR-34c-5p were present in endometritis patients, and they were negatively correlated. Both circ_0001853 and miR-34c-5p alone or in combination had diagnostic value in predicting the progression of endometritis. Transfection of si-circ_0001853 promoted cell proliferation and reduced apoptosis and cellular inflammation levels induced by lipopolysaccharide (LPS) stimulation. There was a direct reciprocal targeting relationship between miR-34c-5p and circ_0001853, and the use of miR-34c-5p inhibitor resisted silencing circ_0001853 promoted cell proliferation and increased the number of apoptotic cells and cellular inflammation levels.
Conclusions
circ_0001853 is involved in endometritis progression through miR-34c-5p, i.e., low circ_0001853 promotes miR-34c-5p-induced proliferation of epithelial cells, reduces apoptosis, and suppresses inflammation levels, preventing disease progression.
{"title":"Down-regulated circ_0001853 inhibits lipopolysaccharide-induced endometritis progression via sponging miR-34c-5p","authors":"Qian Xu, Ailing Peng, Liyun Zhao, Li Wang","doi":"10.1016/j.mcp.2025.102023","DOIUrl":"10.1016/j.mcp.2025.102023","url":null,"abstract":"<div><h3>Background</h3><div>To investigate the diagnostic value and mechanism of action of circular RNA (circ_) circ_0001853 and microRNA (miR) miR-34c-5p in patients with endometritis.</div></div><div><h3>Methods</h3><div>189 patients with endometritis and 176 healthy individuals were included in this study. Venous blood serum was collected from the study subjects and stored temporarily at −80 °C. Real-time quantitative chain polymerase reaction (RT-qPCR) was used to detect circ_0001853 and miR-34c-5p expression, and receiver operating characteristic (ROC) curves assessed the diagnostic value of both in predicting endometritis. Cell counting kit (CCK8) observed cell proliferation, flow cytometry recorded apoptosis, enzyme linked immunosorbent assay (ELISA) monitored inflammatory factor expression, and dual luciferase reporter assay and RNA immunoprecipitation (RIP) verified the relationship between circ_0001853 and miR-34c-5p targeting interactions.</div></div><div><h3>Results</h3><div>High levels of circ_0001853 and low levels of miR-34c-5p were present in endometritis patients, and they were negatively correlated. Both circ_0001853 and miR-34c-5p alone or in combination had diagnostic value in predicting the progression of endometritis. Transfection of si-circ_0001853 promoted cell proliferation and reduced apoptosis and cellular inflammation levels induced by lipopolysaccharide (LPS) stimulation. There was a direct reciprocal targeting relationship between miR-34c-5p and circ_0001853, and the use of miR-34c-5p inhibitor resisted silencing circ_0001853 promoted cell proliferation and increased the number of apoptotic cells and cellular inflammation levels.</div></div><div><h3>Conclusions</h3><div>circ_0001853 is involved in endometritis progression through miR-34c-5p, i.e., low circ_0001853 promotes miR-34c-5p-induced proliferation of epithelial cells, reduces apoptosis, and suppresses inflammation levels, preventing disease progression.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"81 ","pages":"Article 102023"},"PeriodicalIF":2.3,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587915","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 : 2025-03-07DOI: 10.1016/j.mcp.2025.102021
Shaosheng Lou , Wang Yang , Qian Zhao , Yunshan Ouyang , Lingling Cao , Chen Lin
{"title":"Corrigendum to “Identification of circRNA-mediated competing endogenous RNA network involved in the development of cervical cancer” [Mol. Cell. Probes. 78 (2024) 101984]","authors":"Shaosheng Lou , Wang Yang , Qian Zhao , Yunshan Ouyang , Lingling Cao , Chen Lin","doi":"10.1016/j.mcp.2025.102021","DOIUrl":"10.1016/j.mcp.2025.102021","url":null,"abstract":"","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"80 ","pages":"Article 102021"},"PeriodicalIF":2.3,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587914","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 biggest cause of death worldwide is liver cancer. Despite several initiatives and successes in treatment techniques, only a little improvement has been attained. In order to control this cancer, new therapeutic strategies are therefore required. Here, we evaluated the effects of doxorubicin and the milk thistle plant phytochemical Silymarin on liver cancer through apoptosis, autophagy, and Wnt signaling.
Methods
Silymarin both alone and together with doxorubicin was administered to induce cytotoxicity in the H22 cell line. qRT-PCR and Western blot analyses, the genes related to autophagy, Wnt signals, and cell death were examined.
Results
Doxorubicin and Silymarin both individually and combined dramatically slowed down H22 cells growth. Additionally, there was a significant drop in the Bcl-2 protein and a considerable rise in the caspase 8 and Bax proteins. LC3-I, LC3-II, and Beclin 1 have been all shown to be significantly elevated. Moreover, there was a substantial decrease in the expression of genes involved in the Wnt pathway, including cyclin D1, β-catenin, ZEB1, and Twist. The levels of AMPK were decreased in Silymarin with Doxorubicin alone and in combination, whereas VASP, VEGF, and HIF-1a were lowest.
Conclusion
Silymarin may enhance anti-tumor effects of doxorubicin through modulating autophagy, angiogenesis, and apoptosis, in-vitro.
{"title":"Silymarin plus doxorubicin exerts the anti-hepatocellular carcinoma effects via Wnt, apoptosis, autophagy and angiogenesis pathways","authors":"Baohong Yuan , Ruotian Wang , Zehai Gao , Hameed Mirzeei , An-Dong Xiang , Feng Guo","doi":"10.1016/j.mcp.2025.102022","DOIUrl":"10.1016/j.mcp.2025.102022","url":null,"abstract":"<div><h3>Background</h3><div>The biggest cause of death worldwide is liver cancer. Despite several initiatives and successes in treatment techniques, only a little improvement has been attained. In order to control this cancer, new therapeutic strategies are therefore required. Here, we evaluated the effects of doxorubicin and the milk thistle plant phytochemical Silymarin on liver cancer through apoptosis, autophagy, and Wnt signaling.</div></div><div><h3>Methods</h3><div>Silymarin both alone and together with doxorubicin was administered to induce cytotoxicity in the H22 cell line. qRT-PCR and Western blot analyses, the genes related to autophagy, Wnt signals, and cell death were examined.</div></div><div><h3>Results</h3><div>Doxorubicin and Silymarin both individually and combined dramatically slowed down H22 cells growth. Additionally, there was a significant drop in the Bcl-2 protein and a considerable rise in the caspase 8 and Bax proteins. LC3-I, LC3-II, and Beclin 1 have been all shown to be significantly elevated. Moreover, there was a substantial decrease in the expression of genes involved in the Wnt pathway, including cyclin D1, β-catenin, ZEB1, and Twist. The levels of AMPK were decreased in Silymarin with Doxorubicin alone and in combination, whereas VASP, VEGF, and HIF-1a were lowest.</div></div><div><h3>Conclusion</h3><div>Silymarin may enhance anti-tumor effects of doxorubicin through modulating autophagy, angiogenesis, and apoptosis, <em>in-vitro</em>.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"81 ","pages":"Article 102022"},"PeriodicalIF":2.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574471","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 aim of this study was to investigate the clinical significance of microRNA-4449 (miR-4449) in patients attacked by non-small cell lung cancer (NSCLC) undergoing thoracic paravertebral block (TPVB) thoracotomy.
Methods
A total of 122 patients diagnosed with NSCLC and 101 healthy individuals were recruited in this case-control study. Quantitative real-time polymerase reaction time (qRT-PCR) assay was applied to quantify the serum levels of miR-4449 in all participants. To assess the diagnostic potential of miR-4449, receiver operating characteristic (ROC) curves were constructed. Additionally, the prognostic value of miR-4449 was evaluated using Kaplan-Meier method and Cox regression analyses. The possible target genes and related proteins of miR-4449 were predicted via bioinformatics analysis.
Results
MiR-4449 expression was notably reduced in NSCLC patients relative to healthy volunteers (P < 0.001), with the area under the curve (AUC) reaching 0.952, demonstrating its ability to effectively differentiate between NSCLC patients and healthy individuals. Serum levels of miR-4449 were negatively in relation to tumor node metastasis stage and lymph node metastasis (P < 0.05). Moreover, a significant increase in miR-4449 expression was observed in patients following TPVB thoracotomy, as compared to pre-operative levels (P < 0.001). The AUC of 0.884 further highlighted its potential to distinguish between the effective group and the invalid group. Notably, patients expressing high levels of miR-4449 exhibited improved overall survival (P < 0.001), and miR-4449 (P < 0.001, HR = 2.290, 95 % = 1.450–3.615) was identified as an independently prognostic predictor for NSCLC. Bioinformatics analysis of miR-4999 target genes revealed key tumor-associated pathways and proteins, offering valuable insights into its molecular mechanisms in NSCLC.
Conclusion
Serum levels of miR-4449 were significantly decreased in patients with NSCLC and exhibited a correlation with the severity of the tumor. Furthermore, miR-4449 emerged as a potential prognostic biomarker, offering valuable insight into the clinical outcome for NSCLC undergoing TPVB thoracotomy.
{"title":"Clinical value of microRNA-4449 of non-small cell lung cancer patients undergoing thoracic paravertebral block thoracotomy","authors":"Yu Sun , Jiantao Zhang , Licai Zhang , Liquan Qiu , Huayi Zhang","doi":"10.1016/j.mcp.2025.102020","DOIUrl":"10.1016/j.mcp.2025.102020","url":null,"abstract":"<div><h3>Objective</h3><div>The aim of this study was to investigate the clinical significance of microRNA-4449 (miR-4449) in patients attacked by non-small cell lung cancer (NSCLC) undergoing thoracic paravertebral block (TPVB) thoracotomy.</div></div><div><h3>Methods</h3><div>A total of 122 patients diagnosed with NSCLC and 101 healthy individuals were recruited in this case-control study. Quantitative real-time polymerase reaction time (qRT-PCR) assay was applied to quantify the serum levels of miR-4449 in all participants. To assess the diagnostic potential of miR-4449, receiver operating characteristic (ROC) curves were constructed. Additionally, the prognostic value of miR-4449 was evaluated using Kaplan-Meier method and Cox regression analyses. The possible target genes and related proteins of miR-4449 were predicted via bioinformatics analysis.</div></div><div><h3>Results</h3><div>MiR-4449 expression was notably reduced in NSCLC patients relative to healthy volunteers (<em>P</em> < 0.001), with the area under the curve (AUC) reaching 0.952, demonstrating its ability to effectively differentiate between NSCLC patients and healthy individuals. Serum levels of miR-4449 were negatively in relation to tumor node metastasis stage and lymph node metastasis (<em>P</em> < 0.05). Moreover, a significant increase in miR-4449 expression was observed in patients following TPVB thoracotomy, as compared to pre-operative levels (<em>P</em> < 0.001). The AUC of 0.884 further highlighted its potential to distinguish between the effective group and the invalid group. Notably, patients expressing high levels of miR-4449 exhibited improved overall survival (<em>P</em> < 0.001), and miR-4449 (<em>P</em> < 0.001, HR = 2.290, 95 % = 1.450–3.615) was identified as an independently prognostic predictor for NSCLC. Bioinformatics analysis of miR-4999 target genes revealed key tumor-associated pathways and proteins, offering valuable insights into its molecular mechanisms in NSCLC.</div></div><div><h3>Conclusion</h3><div>Serum levels of miR-4449 were significantly decreased in patients with NSCLC and exhibited a correlation with the severity of the tumor. Furthermore, miR-4449 emerged as a potential prognostic biomarker, offering valuable insight into the clinical outcome for NSCLC undergoing TPVB thoracotomy.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"80 ","pages":"Article 102020"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473049","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}