Long non-coding RNA homeobox A11 antisense RNA (HOXA11-AS) promotes retinoblastoma progression via sponging miR-506-3p

Onco Targets Ther. 2019 May 7;12:3509-3517. doi: 10.2147/OTT.S195404. eCollection 2019.

Abstract

Background: Long non-coding RNA homeobox A11 antisense RNA (HOXA11-AS) has been reported to be involved in initiation and development of multiple cancers. However, the detailed biological roles and underlying molecular mechanism of HOXA11-AS remain unclear in retinoblastoma (RB). Herein, the goals of this study were to explore the biological function and the potential mechanism of HOXA11-AS in RB. Materials and methods: The expression of HOXA11-AS in RB tissues and cell lines was detected using real-time PCR (qRT-PCR). Cell proliferation, cycle arrest and apoptosis were measured using a cell counting kit 8 and flow cytometry. The target miRNAs of HOXA11-AS was predicted by Starbase2.0 software and was confirmed using a dual-luciferase reporter assay. Result: We found that HOXA11-AS expression was markedly elevated in RB tissues and cell lines compared to normal retina tissues and human retinal epithelial cells, respectively. Functional analysis showed that knockdown of HOXA11-AS in RB cells significantly suppressed cell proliferation, and induced cell cycle arrest at G1/G0 phase and promoted cell apoptosis. We also found that HOXA11-AS could serve as a competing endogenous RNA (ceRNA) that inhibited miR-506-3p expression, which regulated its downstream target NIMA-related kinase 6 (NEK6) in RB. In addition, miR-506-3p inhibitors partially reversed the effect of HOXA11-AS depletion on proliferation, cycle arrest and apoptosis in RB cells. Conclusion: Taken together, these findings demonstrated that HOXA11-AS could promote RB progression by sponging miR-506-3p, suggesting that HOXA-11-AS might be a potential therapeutic target for RB.

Keywords: LncRNA; apoptosis; miR-506-3p; proliferation; retinoblastoma.