LINC01140 inhibits nonsmall cell lung cancer progression and cisplatin resistance through the miR-4742-5p/TACC1 axis

J Biochem Mol Toxicol. 2022 Jul;36(7):e23048. doi: 10.1002/jbt.23048. Epub 2022 Mar 21.

Abstract

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.

Keywords: LLINC01140; TACC1; cisplatin resistance; miR-4742-5p.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm
  • Fetal Proteins / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • MicroRNAs* / genetics
  • Microtubule-Associated Proteins* / genetics
  • Nuclear Proteins* / genetics
  • RNA, Long Noncoding* / genetics

Substances

  • Fetal Proteins
  • MicroRNAs
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • RNA, Long Noncoding
  • TACC1 protein, human
  • Cisplatin