OIP5‑AS1 modulates epigenetic regulator HDAC7 to enhance non‑small cell lung cancer metastasis via miR‑140‑5p
Jiazhuan Mei, Guiju Liu, Wenhui Wang, Peng Xiao, Dan Yang, Hua Bai, Ruijun Li
Abstract
Long non‑coding RNAs have been reported to be involved in non‑small cell lung cancer (NSCLC) progression. However, whether Opa‑interacting protein 5 antisense RNA 1 (OIP5‑AS1) serves a role in NSCLC remains unclear. Bioinformatics analysis of The Cancer Genome Atlas datasets showed clinical significance and relevance of OIP5‑AS1 in NSCLC. Western blotting and reverse transcription‑quantitative PCR revealed protein and RNA expression levels of the genes [including <em>OIP5‑AS1</em>, microRNA (miR)‑140‑5p, histone deacetylase 7 (<em>HDAC7</em>) and vascular endothelial growth factor A (<em>VEGFA</em>)]. Direct associations between the genes (miR‑140‑5p and OIP5‑AS1, or miR‑140‑5p and HDAC7) were confirmed using a dual‑luciferase reporter assay. Lymphatic vessel formation and invasion ability were detected using a lymphatic vessel formation assay and Transwell invasion assay. OIP5‑AS1 knockdown attenuated lymphatic vessel length and invasion. The role of OIP5‑AS1 was reverted by miR‑140‑5p. HDAC7 and VEGFA are downstream effectors of miR‑140‑5p‑mediated NSCLC metastasis. OIP5‑AS1, miR‑140‑5p, HDAC7 and VEGFA were all dysregulated in human clinical NSCLC tumor tissues. In conclusion, the present results demonstrated a novel mechanism for OIP5‑AS1‑induced metastatic phenotypes of NSCLC via the miR‑140‑5p/HDAC7/VEGFA axis.