Overexpression of HIF-2α-Dependent NEAT1 Promotes the Progression of Non-Small Cell Lung Cancer through miR-101-3p/SOX9/Wnt/β-Catenin Signal Pathway

Abstract

Background/aims: The present study aimed to explore the function of NEAT1 on non-small cell lung cancer (NSCLC), as well as its underlying mechanisms.

Methods: Quantitative realtime PCR (qRT-PCR) was used to measure NEAT1 expression in NSCLC tissues and cells. MTT assay and transwell assay were performed to detect cell proliferation, migration and invasion. Potential target genes were identified via luciferase reporter assay. Protein analysis was performed through western blotting.

Results: The expressions of NEAT1 were significantly higher in both of NSCLC tissues and cells than in normal controls. High expression of NEAT1 was significantly associated with TNM stage (P=0.000) and metastasis (P=0.000). NEAT1 knockdown inhibited the proliferation, migration and invasion of NSCLC cells. Hypoxia induction mediated by HIF-2α promoted EMT and NEAT1 expressions. Moreover, miR-101-3p was a target of NEAT1. We also found that SOX9 was a target of miR-101-3p. Oncogenic function of NEAT1 on NSCLC progression was mediated by miR-101-3p/SOX9/Wnt/β-catenin signaling pathway.

Conclusion: NEAT1 up-regulation induced by HIF-2α over-expression could promote the progression of NSCLC under hypoxic condition. Moreover, NEAT1 also takes part in NSCLC progression via miR-101-3p/SOX9/Wnt/β-catenin axis.

Keywords: Hypoxia; NEAT1; NSCLC; SOX9; Wnt/β-catenin; miR-101-3p.