LINC00852 is associated with poor prognosis in non-small cell lung cancer patients and its inhibition suppresses cancer cell proliferation and chemoresistance via the hsa-miR-145-5p/KLF4 axis.

Abstract

Emerging evidence shows that long non-coding RNAs (lncRNAs) play important roles in human cancer. In the present study, we examined the expression, prognostic implications and functional roles of a lncRNA, LINC00852 in non-small cell lung cancer (NSCLC). LINC00852 expression was examined by quantitative real-time PCR (qRT-PCR) in both NSCLC clinical samples and in vitro NSCLC cell lines. In patients with NSCLC, postoperative overall survival was estimated according to endogenous LINC00852 expression in their cancerous lung tissues. In NSCLC cell line SW900 and H441 cells, LINC00852 was down-regulated to examine its effects on cancer proliferation, cisplatin chemoresistance and cell-cycle transition in vitro, as well as tumorigenicity in vivo. The potential downstream target of LINC00852, the axis of human microRNA-145-5p (hsa-miR-145-5p) and Kruppel-like factor 4 (KLF4) gene, was investigated in NSCLC, by dual-luciferase assay, qRT-PCR and genetic knockdown functional assays. LINC00852 is up-regulated in both NSCLC tumors and NSCLC cell lines. High LINC00852 expression was significantly correlated with NSCLC patients' short overall survival. In NSCLC cell lines, LINC00852 down-regulation had anti-cancer effects by suppressing cancer cell proliferation, cisplatin chemoresistance and cell-cycle transition in vitro, as well as explant growth in vivo. Moreover, the hsa-miR-145-5p/KLF4 axis was demonstrated to be directly regulated by LINC00852 in NSCLC. Inhibiting hsa-miR-145-5p or overexpressing KLF4 could reverse the LINC00852-down-regulation-induced anti-cancer effects on NSCLC cancer cell proliferation and chemoresistance. LINC00852 may be a prognostic biomarker for NSCLC. The epigenetic signaling pathway of LINC00852/hsa-miR-145-5p/KLF4 may be considered as a novel molecular target for fighting NSCLC.