Long Non-coding RNA MIR4435-2HG Promotes Colorectal Cancer Proliferation and Metastasis Through miR-206/YAP1 Axis

Objective: Long noncoding RNAs (lncRNAs) play essential roles in colorectal cancer (CRC) progression. The current study aimed to explore the role of lncRNA MIR4435-2HG in CRC proliferation and metastasis. Methods: Expression of lncRNA MIR4435-2HG and its association with CRC were analyzed using database and clinical specimens. The effects of MIR4435-2HG on cell proliferation, invasion, and migration of CRC were identified after MIR4435-2HG knockdown. The effects of MIR4435-2HG on tumor growth and metastasis were assessed in vivo. The underlying mechanistic associations between MIR4435-2HG, microRNA miR-206, and the transcription factor Yes-associated protein 1 (YAP1) were assessed using bioinformatics and a luciferase reporter gene assay. Results: MIR4435-2HG was highly expressed in CRC tissue compared to that in normal tissue and correlated with poor prognosis. MIR4435-2HG knockdown inhibited CRC cell proliferation, invasion, and migration. Moreover, MIR4435-2HG knockdown inhibited CRC growth and liver metastasis in vitro. We found MIR4435-2HG knockdown reduced YAP1, CTGF, AREG, vimentin, Snail, Slug, and Twist expression but enhanced E-cadherin expression. Functionally, MIR4435-2HG acted as a competing endogenous RNA (ceRNA) to upregulate YAP1 by sponging miR-206. Conclusions: MIR4435-2HG promoted CRC growth and metastasis through miR-206/YAP1 axis and may be used as a prognostic marker and therapeutic target in CRC.