Department of Medical Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
Department of Radiography, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
J Biochem Mol Toxicol. 2022 Jul;36(7):e23048. doi: 10.1002/jbt.23048. Epub 2022 Mar 21.
Recent studies show that lncRNAs participate in drug resistance and nonsmall cell lung cancer (NSCLC) progression. This study aimed to study the roles and mechanisms of long intergenic nonprotein coding RNA 01140 (LINC01140) in regulating NSCLC progression and drug resistance. Real-time quantitative polymerase chain reaction and western blot analysis were used to detect LINC01140, miR-4742-5p, and transforming acidic coiled-coil 1 (TACC1) expression in NSCLC cells. The interaction between two molecules was examined by luciferase reporter and/or RNA immunoprecipitation assays. Cell invasion, apoptosis, and cisplatin cytotoxicity were assessed by transwell invasion assay, flow cytometry analysis, and CCK-8 assay, respectively. LINC01140 was downregulated and miR-4742-5p was upregulated in NSCLC. LINC01140 inhibited miR-4742-5p expression by competitively binding to miR-4742-5p, while miR-4742-5p targeted TACC1 to inhibit TACC1 expression in NSCLC cells. LINC01140 enrichment repressed the invasive potential and cisplatin resistance and triggered apoptosis, which was reversed by miR-4742-5p overexpression. miR-4742-5p inhibition suppressed cell invasion and cisplatin resistance and accelerated apoptosis in NSCLC cells, while TACC1 silencing abolished these effects. Mechanistically, LINC01140 positively regulated TACC1 expression by sponging miR-4742-5p. In conclusion, LINC01140 inhibited NSCLC progression and cisplatin resistance via functioning as a ceRNA for miR-4742-5p to modulate TACC1.
最近的研究表明，lncRNAs 参与了药物耐药和非小细胞肺癌（NSCLC）的进展。本研究旨在研究长非编码 RNA 01140（LINC01140）在调节 NSCLC 进展和耐药性中的作用和机制。实时定量聚合酶链反应和 Western blot 分析用于检测 NSCLC 细胞中的 LINC01140、miR-4742-5p 和转化酸性卷曲螺旋蛋白 1（TACC1）的表达。通过荧光素酶报告基因和/或 RNA 免疫沉淀测定检测两个分子之间的相互作用。通过 Transwell 侵袭实验、流式细胞术分析和 CCK-8 实验分别评估细胞侵袭、凋亡和顺铂细胞毒性。LINC01140 在 NSCLC 中下调，miR-4742-5p 上调。LINC01140 通过竞争性结合 miR-4742-5p 抑制 miR-4742-5p 的表达，而 miR-4742-5p 靶向 TACC1 抑制 NSCLC 细胞中的 TACC1 表达。LINC01140 富集抑制了侵袭潜能和顺铂耐药性，并引发了细胞凋亡，而过表达 miR-4742-5p 则逆转了这种作用。miR-4742-5p 抑制抑制了 NSCLC 细胞的侵袭和顺铂耐药性，并加速了细胞凋亡，而 TACC1 沉默则消除了这些作用。机制上，LINC01140 通过作为 miR-4742-5p 的 ceRNA 来正调控 TACC1 表达。总之，LINC01140 通过作为 miR-4742-5p 的 ceRNA 来抑制 NSCLC 进展和顺铂耐药性，从而调节 TACC1 表达。
