Upregulation of miRNA-450b-5p targets ACTB to affect drug resistance and prognosis of ovarian cancer via the PI3K/Akt signaling pathway.

IF 1.5 4区医学 Q4 ONCOLOGY Translational cancer research Pub Date : 2024-09-30 Epub Date: 2024-09-27 DOI:10.21037/tcr-24-292

Shanzhou Xie, Yuting Su, Jinyan Zhang, Fuqiang Yin, Xia Liu

{"title":"Upregulation of miRNA-450b-5p targets ACTB to affect drug resistance and prognosis of ovarian cancer via the PI3K/Akt signaling pathway.","authors":"Shanzhou Xie, Yuting Su, Jinyan Zhang, Fuqiang Yin, Xia Liu","doi":"10.21037/tcr-24-292","DOIUrl":null,"url":null,"abstract":"Background: Ovarian cancer (OC) is the most malignant gynecologic cancer, and chemoresistance is a major cause of treatment failure in patients with OC. The understanding of microRNA (miRNA) in cancer is limited, and the role of miRNA (miR)-450b-5p in cancer drug resistance is unknown. In this study, we aim to evaluate the role of miR-450b-5p in drug-resistant OC and its underlying mechanisms.Methods: MiR-450b-5p expression was assessed in drug-sensitive and resistant OC cells via quantitative real-time polymerase chain reaction. Cell viability was evaluated using the Cell Counting Kit-8 assay. Progression-free survival (PFS) and overall survival (OS) curves were generated using the Kaplan-Meier method and the log-rank test. Target genes of miR-450b-5p were identified from the Cancer MIRNome database. Co-expressed genes were obtained from The Cancer Genome Atlas and Cancer Genome cBioportal for pathway enrichment and functional clustering analysis.Results: The miRNA-450b-5p expression was significantly increased in A2780 and SKOV3 OC-resistant cells and significantly increased by 17-fold in the A2780-CBP-Lv-miR-450b-5p cells compared to A2780-CBP and A2780-CBP-Lv-NC cells. The up-regulated expression of miR-450b-5p increased the cell viability and half maximal inhibitory concentration (IC50) of A2780 platinum-resistant cells and was associated with poor OS. We obtained 33 potential target genes of miR-450b-5p and beta-actin (ACTB) might be a potential target of miR-450b-5p. Low expression of ACTB predicted poor OS and PFS. We obtained 362 common genes co-expressed with ACTB, which involved 4 critical pathways. PI3K acted as an upstream pathway of the other three pathways, which ultimately responded to drug resistance regulation in OC. The genes enriched in four pathways were cross-analyzed and 13 overlapping genes were obtained. These 13 genes were also significantly and positively co-expressed with ACTB at both protein and mRNA levels.Conclusions: High expression of miRNA-450b-5p might affect drug resistance and prognosis in OC by targeting 13 co-expressed genes of ACTB directly through the PI3K/Akt signaling pathway. Thus, miR-450b-5p might provide a new therapeutic target for drug resistance in OC.","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 9","pages":"4800-4812"},"PeriodicalIF":1.5000,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483453/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tcr-24-292","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/27 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Ovarian cancer (OC) is the most malignant gynecologic cancer, and chemoresistance is a major cause of treatment failure in patients with OC. The understanding of microRNA (miRNA) in cancer is limited, and the role of miRNA (miR)-450b-5p in cancer drug resistance is unknown. In this study, we aim to evaluate the role of miR-450b-5p in drug-resistant OC and its underlying mechanisms.

Methods: MiR-450b-5p expression was assessed in drug-sensitive and resistant OC cells via quantitative real-time polymerase chain reaction. Cell viability was evaluated using the Cell Counting Kit-8 assay. Progression-free survival (PFS) and overall survival (OS) curves were generated using the Kaplan-Meier method and the log-rank test. Target genes of miR-450b-5p were identified from the Cancer MIRNome database. Co-expressed genes were obtained from The Cancer Genome Atlas and Cancer Genome cBioportal for pathway enrichment and functional clustering analysis.

Results: The miRNA-450b-5p expression was significantly increased in A2780 and SKOV3 OC-resistant cells and significantly increased by 17-fold in the A2780-CBP-Lv-miR-450b-5p cells compared to A2780-CBP and A2780-CBP-Lv-NC cells. The up-regulated expression of miR-450b-5p increased the cell viability and half maximal inhibitory concentration (IC₅₀) of A2780 platinum-resistant cells and was associated with poor OS. We obtained 33 potential target genes of miR-450b-5p and beta-actin (ACTB) might be a potential target of miR-450b-5p. Low expression of ACTB predicted poor OS and PFS. We obtained 362 common genes co-expressed with ACTB, which involved 4 critical pathways. PI3K acted as an upstream pathway of the other three pathways, which ultimately responded to drug resistance regulation in OC. The genes enriched in four pathways were cross-analyzed and 13 overlapping genes were obtained. These 13 genes were also significantly and positively co-expressed with ACTB at both protein and mRNA levels.

Conclusions: High expression of miRNA-450b-5p might affect drug resistance and prognosis in OC by targeting 13 co-expressed genes of ACTB directly through the PI3K/Akt signaling pathway. Thus, miR-450b-5p might provide a new therapeutic target for drug resistance in OC.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

miRNA-450b-5p靶向ACTB的上调通过PI3K/Akt信号通路影响卵巢癌的耐药性和预后。

背景：卵巢癌（OC）是恶性程度最高的妇科癌症，化疗耐药是卵巢癌患者治疗失败的主要原因。人们对癌症中的微小RNA（miRNA）了解有限，而miRNA（miR）-450b-5p在癌症耐药性中的作用尚不清楚。本研究旨在评估miR-450b-5p在耐药OC中的作用及其内在机制：方法：通过定量实时聚合酶链反应评估药物敏感和耐药 OC 细胞中 MiR-450b-5p 的表达。使用细胞计数试剂盒-8测定法评估细胞活力。采用 Kaplan-Meier 法和对数秩检验生成无进展生存期（PFS）和总生存期（OS）曲线。miR-450b-5p 的靶基因来自癌症 MIRNome 数据库。共表达基因来自癌症基因组图谱（The Cancer Genome Atlas）和癌症基因组生物门户（Cancer Genome cBioportal），用于通路富集和功能聚类分析：结果：miRNA-450b-5p的表达在A2780和SKOV3 OC耐药细胞中明显增加，与A2780-CBP和A2780-CBP-Lv-NC细胞相比，在A2780-CBP-Lv-miR-450b-5p细胞中增加了17倍。miR-450b-5p的上调表达增加了A2780耐铂细胞的细胞活力和半数最大抑制浓度（IC50），并与不良的OS有关。我们获得了33个miR-450b-5p的潜在靶基因，其中β-肌动蛋白（ACTB）可能是miR-450b-5p的潜在靶基因。ACTB的低表达预示着较差的OS和PFS。我们获得了362个与ACTB共表达的常见基因，其中涉及4个关键通路。PI3K是其他三条通路的上游通路，最终对OC的耐药性调控做出反应。对四条通路中富集的基因进行交叉分析，得到了 13 个重叠基因。这13个基因在蛋白和mRNA水平上也与ACTB呈显著的正共表达：结论：miRNA-450b-5p的高表达可能通过PI3K/Akt信号通路直接靶向ACTB的13个共表达基因，从而影响OC的耐药性和预后。因此，miR-450b-5p可能为OC耐药提供了一个新的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Translational cancer research ONCOLOGY-

CiteScore

2.10

自引率

0.00%

发文量

252

期刊介绍： Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.