文章：

转录组学分析揭示肺腺癌细胞系中与靶向治疗内在耐药性相关的早期改变

Transcriptomic Analysis Reveals Early Alterations Associated with Intrinsic Resistance to Targeted Therapy in Lung Adenocarcinoma Cell Lines

原文发布日期：8 July 2024

DOI: 10.3390/cancers16132490

类型: Article

开放获取: 是

英文摘要：

Lung adenocarcinoma is the most prevalent form of lung cancer, and drug resistance poses a significant obstacle in its treatment. This study aimed to investigate the overexpression of long non-coding RNAs (lncRNAs) as a mechanism that promotes intrinsic resistance in tumor cells from the onset of treatment. Drug-tolerant persister (DTP) cells are a subset of cancer cells that survive and proliferate after exposure to therapeutic drugs, making them an essential object of study in cancer treatment. The molecular mechanisms underlying DTP cell survival are not fully understood; however, long non-coding RNAs (lncRNAs) have been proposed to play a crucial role. DTP cells from lung adenocarcinoma cell lines were obtained after single exposure to tyrosine kinase inhibitors (TKIs; erlotinib or osimertinib). After establishing DTP cells, RNA sequencing was performed to investigate the differential expression of the lncRNAs. Some lncRNAs and one mRNA were overexpressed in DTP cells. The clinical relevance of lncRNAs was evaluated in a cohort of patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA). RT–qPCR validated the overexpression of lncRNAs and mRNA in the residual DTP cells and LUAD biopsies. Knockdown of these lncRNAs increases the sensitivity of DTP cells to therapeutic drugs. This study provides an opportunity to investigate the involvement of lncRNAs in the genetic and epigenetic mechanisms that underlie intrinsic resistance. The identified lncRNAs and CD74 mRNA may serve as potential prognostic markers or therapeutic targets to improve the overall survival (OS) of patients with lung cancer.

摘要翻译： 

肺腺癌是最常见的肺癌类型，而耐药性是其治疗中的重大障碍。本研究旨在探讨长链非编码RNA（lncRNAs）的过表达作为促进肿瘤细胞从治疗开始即产生内在耐药性的机制。药物耐受持续存在细胞（DTP细胞）是癌症细胞的一个亚群，在暴露于治疗药物后仍能存活并增殖，使其成为癌症治疗研究的重要对象。DTP细胞存活的分子机制尚未完全阐明；然而，长链非编码RNA被认为在其中起着关键作用。通过单次暴露于酪氨酸激酶抑制剂（TKIs；厄洛替尼或奥希替尼）后，从肺腺癌细胞系中获得了DTP细胞。建立DTP细胞后，进行了RNA测序以研究lncRNAs的差异表达。一些lncRNAs和一种mRNA在DTP细胞中过表达。在癌症基因组图谱（TCGA）的肺腺癌患者队列中评估了lncRNAs的临床相关性。RT–qPCR验证了残留DTP细胞和肺腺癌活检组织中lncRNAs和mRNA的过表达。敲低这些lncRNAs增加了DTP细胞对治疗药物的敏感性。本研究为探讨lncRNAs参与内在耐药性的遗传和表观遗传机制提供了机会。所鉴定的lncRNAs和CD74 mRNA可能作为潜在的预后标志物或治疗靶点，以提高肺癌患者的总生存期（OS）。

原文链接：

Transcriptomic Analysis Reveals Early Alterations Associated with Intrinsic Resistance to Targeted Therapy in Lung Adenocarcinoma Cell Lines