Translational cancer research最新文献

{"title":"Construction and validation of a cell death-related genes prognosis signature of hepatocellular carcinoma.","authors":"Yue Ma, Che Ismail Che Noh, Rahmawati Pare","doi":"10.21037/tcr-24-1315","DOIUrl":"10.21037/tcr-24-1315","url":null,"abstract":"<p><strong>Background: </strong>The cell death pathway, including apoptosis, autophagy, and necroptosis, plays an essential role in hepatocellular carcinoma (HCC) progression and outcome. However, the integration of the three cell death pathways into a prognostic signature has not yet been reported in HCC. This study aimed to investigate the association among cell death-related genes (CDRGs), prognosis, immune microenvironment, and immune checkpoint.</p><p><strong>Methods: </strong>The RNA expression profiles and corresponding clinical data of HCC were retrieved from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and International Cancer Genome Consortium (ICGC). Univariate Cox regression analysis was performed to identify the relevant prognostic genes, and Lasso Cox regression analysis was employed to calculate the risk score. The relationship between the risk score and clinicopathological characteristics, immune cell infiltration, and immune checkpoint expression was analyzed.</p><p><strong>Results: </strong>A prognostic risk model for HCC was constructed from the identified CDRGs and patients were subgrouped based on risk score. High-risk patients for HCC exhibited a significantly lower overall survival (OS) rate than the low-risk patients. In addition, the receiver operating characteristic (ROC) curve demonstrated the predictive ability of the risk score. Patients in the high-risk group exhibited lower immune cell infiltration and higher expression levels of immune checkpoint molecules.</p><p><strong>Conclusions: </strong>The cell death-related signature established herein provides a valuable predictive tool for survival and holds promise as a potential therapeutic biomarker for HCC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"1157-1170"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>ATP5A1</i> as a potential prognostic biomarker in clear-cell renal cell carcinoma.","authors":"Wei Zhou, Qianli Tang, Jun Wu, Minyu Huang, Qun Huang, Tianzi Qin, Ning Tang, Shasha Gai","doi":"10.21037/tcr-24-1397","DOIUrl":"10.21037/tcr-24-1397","url":null,"abstract":"<p><strong>Background: </strong>Clear cell renal cell carcinoma (ccRCC), a malignant neoplasm originating in the renal tubules, is characterized by extended treatment durations and suboptimal therapeutic outcomes in clinical settings. Adenosine triphosphate (ATP) synthase F1 subunit α (<i>ATP5A1</i>), a subunit of mitochondrial ATP synthase, is integral to the energy metabolism of specific tumors. While prior research has established a link between <i>ATP5A1</i> expression and malignancies, its precise function and clinical significance in ccRCC are yet to be elucidated. The study aims to investigate the role of ATP5A1 in ccRCC and to explore the underlying molecular mechanisms.</p><p><strong>Methods: </strong>The RNA sequencing data from ccRCC and corresponding adjacent tissues were analyzed through The Cancer Genome Atlas to evaluate their diagnostic and prognostic implications. <i>ATP5A1</i> expression in ccRCC was validated using the Human Protein Atlas database. The role of <i>ATP5A1</i> in ccRCC was further characterized through a series of assays, including wound healing, transwell invasion, cell counting kit-8 proliferation, and flow cytometry.</p><p><strong>Results: </strong><i>ATP5A1</i> expression levels were elevated across 17 tumor types while being notably downregulated in 15 others, including ccRCC, esophageal carcinoma, and colon adenocarcinoma. Compared to 293 cells and adjacent normal kidney tissues, renal cancer cells and tissues exhibited a significant reduction in <i>ATP5A1</i> expression. An inverse relationship was observed between <i>ATP5A1</i> expression and both the clinical stage and histological grade of ccRCC, yet it is positively associated with improved prognosis. Silencing <i>ATP5A1</i> expression enhanced the malignant biological properties of ccRCC, while its upregulation inhibited these effects. Furthermore, <i>ATP5A1</i> knockdown activated the Wnt/β-catenin signaling pathway, whereas its overexpression resulted in pathway suppression.</p><p><strong>Conclusions: </strong>Collectively, this study indicates that <i>ATP5A1</i> may serve as a potential biomarker for the diagnosis, prognosis, and therapeutic targeting of ccRCC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"1246-1264"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-sensitivity modified Glasgow prognostic score (HS-mGPS) is a prognostic biomarker for small duct-type intrahepatic cholangiocarcinoma-a retrospective cohort study.","authors":"Xintao He, Zixin Liang, Shuo Zhang, Youxiang Ding, Xiaoping Qian, Hongyan Wu, Jun Chen","doi":"10.21037/tcr-24-917","DOIUrl":"10.21037/tcr-24-917","url":null,"abstract":"<p><strong>Background: </strong>Serum biomarkers are often used as part of preoperative prediction strategies to help assess a patient's surgical risk and prognosis. The high-sensitivity modified Glasgow prognostic score (HS-mGPS) has been shown to offer better predictive accuracy compared to the traditional Glasgow prognostic score (GPS) and the modified Glasgow prognostic score (mGPS) in various cancers, but its ability to predict outcomes in patients with resected intrahepatic cholangiocarcinoma (ICC) has not been well-studied. The aim of the study was to investigate the prognostic value of HS-mGPS in ICC and its subtypes.</p><p><strong>Methods: </strong>This study was a single-center retrospective study. All patients who were pathologically diagnosed with ICC after surgery in Nanjing Drum Tower Hospital from 2012 and 2022. Relevant laboratory data such as serum C-reactive protein (CRP), albumin (ALB), neutrophils, lymphocytes, and platelets were included. Overall survival (OS) information was collected, serum CRP and ALB level were used for scoring GPS, mGPS and HS-mGPS. Univariate and multivariate analyses were conducted to identify factors influencing prognosis by using Kaplan-Meier (KM) curve and Cox proportional hazards models. Additionally, through histological analysis, ICC was classified into large duct type (LD-type) and small duct type (SD-type), and the performance of the three scoring systems in these subtypes was examined.</p><p><strong>Results: </strong>A total of 185 patients were included in this study, 57 cases were of the LD-type, and 128 cases were of the SD-type. Tumor subtypes was a significant factor influencing prognosis for all ICC patients [hazard ratio (HR) =1.76, 95% confidence interval (CI): 1.036-2.994, P=0.04]. HS-mGPS demonstrated a better ability to predict outcomes compared to GPS and mGPS, and was an independent prognostic factor of OS (HR =2.1, 95% CI: 1.001-4.374, P=0.049). HS-mGPS was also more effective in predicting prognosis for SD-type ICC compared to GPS and mGPS (HR =3.13, 95% CI: 1.018-9.604, P=0.046), while it was ineffective for LD-type ICC. Further analysis revealed that SD-type ICC with higher HS-mGPS scores typically had larger tumors and poorer differentiation, while LD-type ICC showed no significant differences.</p><p><strong>Conclusions: </strong>HS-mGPS provides a more accurate prognostic indication for SD-type, but its effectiveness for LD-type requires further investigation with larger sample sizes. Therefore, for preoperatively biopsy-diagnosed SD-type ICC, the HS-mGPS has a certain level of prognostic predictive potential.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"1297-1310"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nomogram for predicting survival in breast cancer with lung metastasis based on SEER data.","authors":"Cheng-Liang Chen, Ni-Ya Chen, Shuo Wu, Xiao Lin, Xin-Wei He, Ying Qiu, Di-Xin Xue, Jie Li, Meng-Die He, Xi-Xi Dong, Wei-Ya Zhuang, Mei-Zhen Liang","doi":"10.21037/tcr-24-1047","DOIUrl":"10.21037/tcr-24-1047","url":null,"abstract":"<p><strong>Background: </strong>The incidence of breast cancer (BC) has been steadily increasing, highlighting the need for a predictive model to assess the survival prognosis of BC patients. The objective of this research was to formulate a prognostic nomogram framework tailored to forecast survival among individuals diagnosed with BC with lung metastasis (BCLM).</p><p><strong>Methods: </strong>Our information was sourced from the Surveillance, Epidemiology, and End Results (SEER) database. Individuals who were diagnosed with BC from 2010 to 2015 were selected. The 4,309 collected participants were randomly separated into a training cohort (n=3,231) and a validation cohort (n=1,078). In this study, age, marital status, race, tumor location, laterality, type of primary surgery, surgical margin, tumor grade, tumor (T) stage, node (N) stage, as well as the use of radiotherapy and chemotherapy, were identified as potential prognostic factors. The overall survival (OS) and breast cancer-specific survival (CSS) were defined as the primary endpoints of this study. Univariate and multivariate analyses were conducted to assess the impact of different factors on prognosis. Structured nomograms were developed to improve the prediction of OS and CSS. The concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were employed to estimate the performance of the nomogram.</p><p><strong>Results: </strong>The nomograms incorporated age, marital status, race, primary surgery or not, BC subtype, grade, T stage, and the use of chemotherapy or not. The C-index for OS was 0.77, and it was 0.77 in CSS for the training group. The C-indexes for the control group of OS and CSS prediction were 0.78 and 0.78, respectively. ROC curves, calibration plots, and DCA curves displayed excellent predictive validity. The results indicate a median survival time of 1.67 years [95% confidence interval (CI): 1.58-1.83], with a total of 3,640 deaths recorded. Survival time was found to be associated with factors such as age, marital status, race, whether primary site surgery was performed, BC subtype, tumor grade, T stage, and the administration of chemotherapy.</p><p><strong>Conclusions: </strong>Nomograms were created to predict OS and CSS for individuals diagnosed with BCLM. The nomogram has a reliable and valid prediction power; it could perhaps assist physicians in calculating patients' mortality risk.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"808-826"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accelerated hypofractionated chemoradiation followed by stereotactic ablative radiotherapy boost for locally advanced, unresectable non-small cell lung cancer.","authors":"Urs M Weber, Alexander S Watson, Brian D Kavanagh, Paul A Bunn","doi":"10.21037/tcr-24-1869","DOIUrl":"10.21037/tcr-24-1869","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"676-678"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating white blood cell traits, chemokines and small cell lung cancer risk: a Mendelian randomization study.","authors":"Huizhong Zhu, Chenyang Wang, Teng Ma","doi":"10.21037/tcr-24-1211","DOIUrl":"10.21037/tcr-24-1211","url":null,"abstract":"<p><strong>Background: </strong>Small cell lung cancer (SCLC) commonly originates in the context of persistent inflammation. The impact of white blood cell (WBC) counts and the presence of infiltrating inflammatory cytokines in relation to tumor initiation, progression, and treatment response in SCLC remains uncertain. To elucidate the potential relationships of circulating WBCs and chemokines with SCLC, we conducted a univariable (UVMR) and multivariable Mendelian randomization (MVMR) study.</p><p><strong>Methods: </strong>We conducted a two-sample Mendelian randomization (MR) investigation to evaluate the causal impact of circulating WBCs and chemokines on the risk of SCLC. The genetic data for SCLC were derived from a genome-wide association study (GWAS) involving 24,108 participants, including 2,664 cases and 21,444 controls of European ancestry. The genetic variances of circulating WBCs and chemokines were also from GWAS. In the analysis of UVMR, the primary method employed was the inverse variance weighted (IVW) method. To infer causality, robust adjusted profile scores, weighted median (WM), and MR Egger were employed as supplementary methods. To ensure the robustness of the MR results, sensitivity analyses, including the Cochran <i>Q</i> test, Egger intercept test, and leave-one-out analysis, were conducted. Furthermore, MVMR was carried out to assess the direct causal effects of WBCs and chemokines on the risk of SCLC.</p><p><strong>Results: </strong>Using two-sample MR, we found that genetic predisposition to CD45RA⁺ CD8⁺ T cell, CD39⁺ CD4⁺ T cell, chemokine (C-X-C motif) ligand 16 (CXCL16) was associated with an increased risk of SCLC. There were suggestive inverse associations of genetically predicted dendritic cell, CD14^- CD16⁺ monocyte, P-selectin glycoprotein ligand 1 (PSGL-1) and C-C motif chemokine ligand 3 (CCL3) with SCLC risk. MVMR further confirmed that CXCL16 exerted a direct effect on SCLC, while CD14^- CD16⁺ monocyte and PSGL-1 indicated that they are protective in SCLC.</p><p><strong>Conclusions: </strong>Using two-sample MR, we found that genetic predisposition to CD45RA⁺ CD8⁺ T cell, CD39⁺ CD4⁺ T cell, CXCL16 was associated with an increased risk of SCLC. There were suggestive inverse associations of genetically predicted dendritic cell, CD14^- CD16⁺ monocyte, PSGL-1 and CCL3 with SCLC risk. MVMR further confirmed that CXCL16 exerted a direct effect on SCLC, while CD14^- CD16⁺ monocyte and PSGL-1 indicated that they are protective in SCLC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"1205-1213"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of the immunological implication and prognostic value of MEAK7 in non-small cell lung cancer.","authors":"Jing-Yu Miao, Zhen Lin","doi":"10.21037/tcr-24-1448","DOIUrl":"10.21037/tcr-24-1448","url":null,"abstract":"<p><strong>Background: </strong>The mechanistic target of rapamycin (mTOR)-associated protein Eak-7 homolog (MEAK7) is widely involved in the occurrence and development of various diseases, including tumors. However, the role of MEAK7 in non-small cell lung cancer (NSCLC) and its underlying mechanism in the tumor microenvironment remain unclear. The purpose of this paper is to explore the role of MEAK7 in the prognosis of NSCLC.</p><p><strong>Methods: </strong>The expression levels of <i>MEAK7</i> were examined through the utilization of The Cancer Genome Atlas (TCGA) and the genotype-tissue expression project's pan-cancer dataset. Within this context, the relationships between <i>MEAK7</i> expression and various clinical features, as well as patient outcomes, were assessed using a comprehensive array of bioinformatics resources. Additionally, the link between <i>MEAK7</i> expression and the infiltration of immune cells was investigated employing CIBERSORT and ESTIMATE methodologies. Gene set enrichment analysis was performed to determine immune responses. Finally, the patient response to immunotherapy was predicted using the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and immune checkpoint score.</p><p><strong>Results: </strong><i>MEAK7</i> was highly expressed in many types of tumors including lung adenocarcinoma and lung squamous cell carcinoma. Elevated <i>MEAK7</i> expression was found to correlate with several key characteristics, including sex, age, the presence of metastasis, and pathological staging, and was identified as a significant predictor of poor prognosis in individuals with lung cancer. Subsequent analyses revealed a positive association between heightened <i>MEAK7</i> levels and the infiltration of immune cells, as well as the expression profiles of a variety of immune cell markers. <i>MEAK7</i> was closely linked to the pathways involved in immune regulation. Interestingly, patients with elevated <i>MEAK7</i> expression levels were sensitive to immunotherapy.</p><p><strong>Conclusions: </strong>These findings provide compelling evidence that <i>MEAK7</i> may be involved in the progression of lung cancer and become a potential therapeutic target.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"1085-1100"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciding where Trop-2 directed antibody drug conjugates work in non-small cell lung cancer: the not so straightforward road.","authors":"Robert Hsu","doi":"10.21037/tcr-24-1870","DOIUrl":"10.21037/tcr-24-1870","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"679-684"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The emerging role of transmembrane proteins in tumorigenesis and therapy.","authors":"Chenlu Shen, Xiao Han, Qi Liu, Tao Lu, Weiwei Wang, Xinyi Wang, Zhimin Ou, Shengjie Zhang, Xiangdong Cheng","doi":"10.21037/tcr-24-1660","DOIUrl":"10.21037/tcr-24-1660","url":null,"abstract":"<p><p>Transmembrane proteins (TMEMs) are a kind of proteins that can cross the phospholipid bilayer one or multiple times and remain permanently anchored. They are involved in the regulation of many biological functions, and their dysregulation is associated with many human diseases and even cancer. Abnormal expression alterations of TMEMs widely exist in tumor tissues compared with paracancerous tissues. They are associated with the clinicopathological features of cancer patients by promoting or inhibiting the development of cancer, thus affecting survival. This review summarized the structure and physiological functions of TMEMs, as well as their roles in tumorigenesis, such as cell proliferation, apoptosis, autophagy, adhesion, metastasis, metabolism and drug resistance. In addition, we elaborated on the potentiality of TMEMs for tumor immunity. Moreover, the advances of TMEMs were subsequently retrospected in several common types of human cancers, including breast cancer, gastric cancer, and lung cancer. Subsequently, we outlined the targeted therapeutic strategies against TMEMs proposed based on existing studies. To date, there are still many TMEMs whose functions and mechanisms have not been well known due to their special structures. Since the important roles TMEMs plays in the development of human cancers, it is urgent to portray their structure and function in carcinogenesis, providing potential biomarkers for cancer patients in the future.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"1447-1466"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The miR-155-5p/<i>FBXO11</i> axis inhibits the progression of gastric cancer via the mTOR pathway.","authors":"Tao Yuan, Haiyan Liu, Fangfang Li, Qingyue Meng, Yajuan Wang, Mei Yuan","doi":"10.21037/tcr-2025-8","DOIUrl":"10.21037/tcr-2025-8","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is a leading cause of cancer-related death. MicroRNAs (miRNAs or miRs) play a crucial role in the pathology of GC, including cell proliferation, invasion, and metastasis. In this study, genes targeted by miR-155-5p were predicted using bioinformatic tools. We found that the expression of miR-155-5p in GC cell lines differed relative to the expression of F-box protein 11 (<i>FBXO11</i>), which is involved in the regulation of cellular processes. This study sought to examine the function of miR-155-5p and the precise mechanism underlying its regulatory function in modulating proliferation and apoptosis in GC.</p><p><strong>Methods: </strong>The luciferase reporter assay results showed that miR-155-5p bound directly to the three prime untranslated region (3'-UTR) of <i>FBXO11</i>, which further downregulated <i>FBXO11</i> expression. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western-blot analyses confirmed that miR-155-5p negatively regulated the messenger RNA (mRNA) and protein expression of <i>FBXO11</i>. The effects of <i>FBXO11</i> on cell proliferation and apoptosis in GC cell lines was further examined using Cell Counting Kit-8 (CCK-8) and flow cytometry.</p><p><strong>Results: </strong>We found that <i>FBXO11</i> promoted proliferation and decreased apoptosis in GC cells. Conversely, rescue experiments showed that the knockdown of <i>FBXO11</i> limited the effects of miR-155-5p on the proliferation and apoptosis of GC cells, providing further evidence that <i>FBXO11</i> is a functional target of miR-155-5p. Further, the overexpression of miR-155-5p inhibited cell growth via the targeted inhibition of <i>FBXO11</i> that regulated mammalian target of rapamycin (mTOR) signaling pathway in the GC cells.</p><p><strong>Conclusions: </strong>Overall, these results showed that miR-155-5p may serve as a tumor suppressor in GC and that the miR-155-5p/<i>FBXO11</i> axis regulates tumor progression via the mTOR signaling pathway. Consequently, our findings may lead to the development a novel treatment strategy for GC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"1375-1387"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}