Positive feedback loop of lncRNA HOXC-AS2/miR-876-5p/ZEB1 to regulate EMT in glioma

Onco Targets Ther. 2019 Sep 16:12:7601-7609. doi: 10.2147/OTT.S216134. eCollection 2019.

Abstract

Purpose: Growing evidence has valued the diagnostic and therapeutic ability of long non-coding RNAs (lncRNAs) in various human tumors including glioma. Here, we investigated the biological function and potential mechanism of a novel cancer-related lncRNA, HOXC-AS2, in glioma.

Materials and methods: The expression of lncHOXC-AS2 was detected using qRT-PCR in glioma cells and tissues. A series of in vitro studies were performed to analyze the biological function of lncHOXC-AS2. Dual-luciferase reporter, RIP was used to determine the relation between lncHOXC-AS2, miR-876-5p and ZEB1. CHIP assay was performed to investigate the transcriptional regulation of HOXC-AS2.

Results: We found HOXC-AS2 was upregulated in glioma cells and tissues. Depletion of HOXC-AS2 was associated with the inhibition of migration, invasion and EMT process in glioma cells. Mechanism, HOXC-AS2 can sponge miR-876-5p to affect ZEB1 expression. Meanwhile, ZEB1 can bind promoter region of HOXC-AS2 and regulate HOXC-AS2 at transcriptional level.

Conclusion: Our results conclude that HOXC-AS2/miR-876-5p/ZEB1 constitutes a positive feedback loop to regulate EMT in GBM, providing a potential therapeutic target for glioma.

Keywords: HOXC-AS2; competing endogenous RNA; epithelial–mesenchymal transition; glioma.