Wu Juan, Chen Ru, Shen Huiqing, Yan Ting, Qian Yu, Zhang Yaping, Huang Zhuoya, Kong Pengzhou, Pang Min, Zhang Xinri
Department of Respiratory and Critical Care Medicine, The First Hospital, Shanxi Medical University, Taiyuan, China.
Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research on Esophageal Cancer, Shanxi Medical University, Taiyuan, China.
Front Oncol. 2021 Mar 30;11:626605. doi: 10.3389/fonc.2021.626605. eCollection 2021.
Ivosidenib is an isocitrate dehydrogenase mutant inhibitor that the US Food and Drug Administration recently approved for the treatment of leukemia. Studies suggested that ivosidenib may inhibit the progression of non-small cell lung cancer (NSCLC). In the present study, we explored RNAs and their potential regulatory mechanisms by which ivosidenib treats NSCLC cells. We used MTT assays, Transwell assays, and flow cytometry to measure the anti-tumor effects of ivosidenib in NSCLC cells. We performed whole transcriptome sequencing to determine differentially expressed mRNAs (DE-mRNAs) and non-coding RNAs (ncRNA). We used GO and KEGG pathway enrichment analyses to identify the functions and potential mechanisms. According to miRNA target interactions, we constructed a competing endogenous network. Ivosidenib inhibited the proliferation, invasion, and migration of NSCLC cells and inhibited tumor growth . We identified 212 DE-mRNAs, four DE-miRNAs, and 206 DE-lncRNAs in ivosidenib-treated NSCLC cells compared to untreated NSCLC cells. DE-mRNAs were significantly enriched in the cancer-associated pathways, including the TGF-β signaling pathway, the PI3K-Akt signaling pathway, the Jak-STAT signaling pathway, the MAPK signaling pathway, the Rap1 signaling pathway, and cell adhesion molecules. Based on the competing endogenous RNA hypothesis, we constructed lncRNA-miRNA-mRNA networks to elucidate the regulatory relationships between mRNA and ncRNA. We found that qRT-PCR results showed corresponding expression trends of differential genes with sequencing data. Our results provide insights into the molecular basis of ivosidenib suppression of NSCLC.
艾伏尼布是一种异柠檬酸脱氢酶突变体抑制剂，美国食品药品监督管理局最近批准其用于治疗白血病。研究表明，艾伏尼布可能抑制非小细胞肺癌（NSCLC）的进展。在本研究中，我们探索了艾伏尼布治疗NSCLC细胞的RNA及其潜在调控机制。我们使用MTT法、Transwell法和流式细胞术来检测艾伏尼布对NSCLC细胞的抗肿瘤作用。我们进行了全转录组测序以确定差异表达的mRNA（DE-mRNA）和非编码RNA（ncRNA）。我们使用GO和KEGG通路富集分析来确定其功能和潜在机制。根据miRNA靶标相互作用，我们构建了一个竞争性内源网络。艾伏尼布抑制了NSCLC细胞的增殖、侵袭和迁移，并抑制了肿瘤生长。与未处理的NSCLC细胞相比，我们在经艾伏尼布处理的NSCLC细胞中鉴定出212个DE-mRNA、4个DE-miRNA和206个DE-lncRNA。DE-mRNA在癌症相关通路中显著富集，包括TGF-β信号通路、PI3K-Akt信号通路、Jak-STAT信号通路、MAPK信号通路、Rap1信号通路和细胞黏附分子。基于竞争性内源RNA假说，我们构建了lncRNA-miRNA-mRNA网络以阐明mRNA和ncRNA之间的调控关系。我们发现qRT-PCR结果显示差异基因的表达趋势与测序数据一致。我们的结果为艾伏尼布抑制NSCLC的分子基础提供了见解。
