MicroRNA-139-5p regulates NSCLC tumorigenicity by targeting TOP2A

Abstract

AbstractMicroRNA-139-5p (miR-139-5p) plays a crucial role in cancer’s onset and progression and is considered a tumor suppressor gene. However, the biological functions and mechanism of miR-139-5p in the tumorigenicity in Non-small cell lung cancer (NSCLC) has received insufficient investigation. We investigated the miR-139-5p expression in lung cancer tissues and the adjacent normal lung tissues, in 54 NSCLC patients. Additionally, the miR-139-5p target gene was predicted by bioinformatics analysis and then confirmed by a dual-luciferase reporter assay. The biological functions of miR-139-5p and the target gene have been investigated, in both in vitro and in vivo studies. Finally, the anti-tumor effects of miR-139-5p were corroborated by tumor formation assay in nude mice and progression-free survival analysis in another 144 NSCLC patients.MiR-139-5p was down-regulated, and inversely correlated with DNA topoisomerase II alpha (TOP2A), in both NSCLC tissues and cells. In vitro, miR-139-5p overexpression suppressed proliferation, migration, and invasion by down-regulating TOP2A in normal human bronchial epithelioid cells and NSCLC cell lines. It also induced apoptosis in NSCLC cell lines. In vivo, miR-139-5p up-regulation and the TOP2A mRNA down-regulation were significantly correlated, with longer progression-free survival times in 144 NSCLC patients. Moreover, miR-139-5p overexpression mitigated the xenograft tumor formation. MiR-139-5p inhibited growth and metastasis in NSCLC cell lines via direct TOP2A targeting. Low miR-139-5p expression showed a significant correlation with poor prognosis in NSCLC patients. These results highlight the effect of miR-139-5p on NSCLC, suggesting that miR-139-5p is a promising biomarker for NSCLC prognosis and an exceptional candidate for further therapeutic exploration.