Long Noncoding RNA ZFPM2-AS1 Knockdown Restrains the Development of Retinoblastoma by Modulating the MicroRNA-515/HOXA1/Wnt/β-Catenin Axis.

PURPOSE

The tumor-initiating function of long non-coding RNA (lncRNA), zinc finger protein multitype 2 antisense RNA 1 (ZFPM2-AS1) was reported in lung cancer, yet the relevance of ZFPM2-AS1 in retinoblastoma (RB), a malignancy representing 2.5% to 4% incidence of cancers among children, has not been elucidated. Thus, we attempted to assess the effect of ZFPM2-AS1 and underlying mechanism in RB progression.

METHODS

First, comparing the differentially expressed lncRNAs in normal retinal tissues as well as RB tissues, the target lncRNA ZFPM2-AS1 was screened out. We then assayed the ZFPM2-AS1 expression in three RB cell lines, and carried out methylthiazol tetrazolium (MTT), transwell assays, and flow cytometric analyses to examine the role of si-ZFPM2-AS1 on cell behaviors. Following online database predication, the correlations between ZFPM2-AS1 and microR-515 (miR-515) or homeobox A1 (HOXA1) were corroborated by dual-luciferase reporter gene assays. Quantitative real-time PCR along with Western blot assays was fulfilled to ascertain the expression of relevant genes.

RESULTS

ZFPM2-AS1 was significantly overexpressed in RB tissues and cell lines, and ZFPM2-AS1 silencing curtailed the growth and metastasis of RB cells both in vitro and in vivo. Bioinformatic websites and dual-luciferase reporter gene assays disclosed that ZFPM2-AS1 might perform as a competing endogenous RNA for miR-515 and positively correlate with HOXA1 to activate the Wnt/β-catenin signaling pathway.

CONCLUSION

Altogether, these data demonstrated that ZFPM2-AS1 interacted with HOXA1 to promote RB development via mediating miR-515, establishing a promising therapeutic biomarker for RB and prognosis.