KRT14 knockdown reduces cisplatin resistance by lowering LRP11 expression levels in cisplatin-resistant ovarian cancer cell lines.

IF 1.5 4区医学 Q4 ONCOLOGY

Translational cancer research Pub Date : 2025-03-30 Epub Date: 2025-03-14 DOI:10.21037/tcr-24-1795

Zequn Liu, Tingsong Weng, Mi Cheng, Tingying Lei, Du Xiao, Qiong Deng, Tianmei Wu

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引用次数: 0

Abstract

Background: Platinum resistance is a major cause of mortality in patients with advanced ovarian cancer. Understanding the mechanisms underlying this resistance is essential for developing effective treatments to improve patient survival. Therefore, this study aimed to explore the role and mechanisms of keratin 14 (KRT14) in regulating cisplatin resistance in ovarian cancer.

Methods: We utilized quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting to measure messenger RNA (mRNA) and protein expression levels, respectively. Cisplatin-resistant cell lines (SK-OV-3/DDP and A2780/DDP) were transfected with small interfering RNA (siRNA) targeting KRT14 (si-KRT14) or a plasmid containing low-density lipoprotein receptor-related protein 11 (LRP11) to knock down KRT14 or overexpress LRP11, respectively. Differentially expressed mRNAs were identified using Illumina RNA sequencing. Cell viability and half-maximal inhibitory concentration (IC₅₀) values were determined via cell counting kit-8 (CCK-8) assays, while apoptosis was assessed using flow cytometry and Hoechst 33258 staining.

Results: KRT14 mRNA and protein levels were significantly higher in SK-OV-3/DDP and A2780/DDP cells compared with their parental counterparts. KRT14 knockdown reduced the IC₅₀ values, increased apoptosis, and decreased the levels of the multidrug resistance (MDR)-related proteins P-glycoprotein (P-gp) and MDR-associated protein 1 (MRP1). KRT14 knockdown in SK-OV-3/DDP and A2780/DDP cells revealed 24 differentially expressed mRNAs. Further analysis revealed that KRT14 knockdown notably reduced LRP11 expression. LRP11 overexpression increased IC₅₀ values, suppressed apoptosis, and enhanced MDR-related protein expression, thus counteracting the effects of KRT14 knockdown.

Conclusions: Cisplatin-resistant ovarian cancer cell lines revealed elevated KRT14 expression. KRT14 knockdown reduced cisplatin resistance by lowering LRP11 expression. Therefore, KRT14 may play a crucial role in mediating cisplatin resistance in ovarian cancer.

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KRT14敲低通过降低顺铂耐药卵巢癌细胞系中LRP11的表达水平来降低顺铂耐药。

背景：铂耐药是晚期卵巢癌患者死亡的主要原因。了解这种耐药性的潜在机制对于开发有效的治疗方法以提高患者生存率至关重要。因此，本研究旨在探讨角蛋白14 （keratin 14, KRT14）在卵巢癌顺铂耐药调控中的作用及机制。方法：采用定量逆转录-聚合酶链反应（qRT-PCR）和western blotting分别检测mRNA和蛋白的表达水平。顺铂耐药细胞系SK-OV-3/DDP和A2780/DDP分别转染靶向KRT14 （si-KRT14）的小干扰RNA （siRNA）或含有低密度脂蛋白受体相关蛋白11 （LRP11）的质粒，分别敲低KRT14或过表达LRP11。利用Illumina RNA测序技术鉴定差异表达mrna。通过细胞计数试剂盒-8 （CCK-8）检测细胞活力和半最大抑制浓度（IC50），通过流式细胞术和Hoechst 33258染色检测细胞凋亡。结果：SK-OV-3/DDP和A2780/DDP细胞中KRT14 mRNA和蛋白水平显著高于亲本。KRT14敲低可降低IC50值，增加细胞凋亡，降低多药耐药（MDR）相关蛋白p -糖蛋白（P-gp）和MDR相关蛋白1 （MRP1）水平。在SK-OV-3/DDP和A2780/DDP细胞中，KRT14敲低显示了24种差异表达的mrna。进一步分析发现，KRT14敲低显著降低了LRP11的表达。LRP11过表达增加IC50值，抑制细胞凋亡，增强mdr相关蛋白表达，从而抵消KRT14敲低的影响。结论：顺铂耐药卵巢癌细胞系显示KRT14表达升高。KRT14敲除通过降低LRP11的表达降低顺铂耐药。因此，KRT14可能在介导卵巢癌顺铂耐药中发挥了至关重要的作用。

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

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.