Transcriptome analysis of an AKT inhibitor-resistant endometrial cancer cell line.

IF 3.6 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pharmacological Reports Pub Date : 2024-04-01 Epub Date: 2024-03-13 DOI:10.1007/s43440-024-00581-w

Takafumi Onishi, Tsuyoshi Takashima, Kazuki Shibahara, Shoji Takagi, Shinichi Tanaka, Michihiro Mori, Hirokazu Odashima, Yukihiko Osawa, Manabu Hattori

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引用次数: 0

Abstract

Background: Drug resistance in endometrial cancer (EC) is a serious problem and a barrier to improving prognosis. The PI3K/AKT/mTOR pathway is highly activated in EC and can serve as a potential therapeutic target. Inhibitors against AKT have been developed, but resistance to these inhibitors is a concern. This study aimed to establish AKT inhibitor resistant cell lines and identify differentially expressed genes (DEGs) between parental and AKT inhibitor resistant cell lines to understand the mechanism of drug resistance to AKT inhibitors in EC.

Methods: The sensitivity of eight EC cell lines to AKT inhibitor was analyzed. One of them was used to establish a drug-resistant cell line. DEGs were examined using RNA sequencing (RNA-seq). Furthermore, DEGs were comprehensively analyzed to identify hub genes. Hub genes were evaluated using quantitative real-time polymerase chain reaction.

Results: RNA-seq identified 617 DEGs. Hub genes were selected using bioinformatics analysis. The top 10 hub genes were TNF, CDH1, CCND1, COL1A1, CDH2, ICAM1, CAV1, THBS1, NCAM1, and CDKN2A. Relative mRNA expression was significantly upregulated for TNF, CDH1, CCND1, THBS1, p16^INK4a, and p14^ARF and significantly downregulated for CDH2, ICAM1, and NCAM1 in borussertib-resistant EC cell line.

Conclusions: Drug resistance to AKT inhibitors may depend on genes related to cell adhesion-mediated resistance and transforming growth factor β signaling.

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AKT 抑制剂耐药子宫内膜癌细胞系的转录组分析。

背景：子宫内膜癌（EC）的耐药性是一个严重问题，也是改善预后的障碍。PI3K/AKT/mTOR通路在子宫内膜癌中被高度激活，可作为潜在的治疗靶点。目前已开发出针对AKT的抑制剂，但这些抑制剂的耐药性令人担忧。本研究旨在建立AKT抑制剂耐药细胞系，并鉴定亲本细胞系和AKT抑制剂耐药细胞系之间的差异表达基因（DEGs），以了解EC对AKT抑制剂耐药的机制：方法：分析了8个EC细胞系对AKT抑制剂的敏感性。方法：分析了8个EC细胞系对AKT抑制剂的敏感性，其中一个细胞系被用来建立耐药细胞系。使用 RNA 测序（RNA-seq）检测 DEGs。此外，还对 DEGs 进行了综合分析，以确定枢纽基因。利用实时定量聚合酶链反应对枢纽基因进行评估：结果：RNA-seq鉴定出617个DEGs。通过生物信息学分析筛选出了枢纽基因。前10个枢纽基因是TNF、CDH1、CCND1、COL1A1、CDH2、ICAM1、CAV1、THBS1、NCAM1和CDKN2A。在博路赛替布耐药的EC细胞系中，TNF、CDH1、CCND1、THBS1、p16INK4a和p14ARF的相对mRNA表达明显上调，而CDH2、ICAM1和NCAM1则明显下调：结论：AKT抑制剂的耐药性可能取决于与细胞粘附介导的耐药性和转化生长因子β信号转导相关的基因。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacological Reports 医学-药学

CiteScore

8.40

自引率

0.00%

发文量

审稿时长

6 months

期刊介绍： Pharmacological Reports publishes articles concerning all aspects of pharmacology, dealing with the action of drugs at a cellular and molecular level, and papers on the relationship between molecular structure and biological activity as well as reports on compounds with well-defined chemical structures. Pharmacological Reports is an open forum to disseminate recent developments in: pharmacology, behavioural brain research, evidence-based complementary biochemical pharmacology, medicinal chemistry and biochemistry, drug discovery, neuro-psychopharmacology and biological psychiatry, neuroscience and neuropharmacology, cellular and molecular neuroscience, molecular biology, cell biology, toxicology. Studies of plant extracts are not suitable for Pharmacological Reports.