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

Invest Ophthalmol Vis Sci. 2020 Jun 3;61(6):41. doi: 10.1167/iovs.61.6.41.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Child
  • Child, Preschool
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Infant
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Retinal Neoplasms / genetics*
  • Retinal Neoplasms / metabolism
  • Retinal Neoplasms / pathology
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Wnt Signaling Pathway / genetics*
  • beta Catenin / biosynthesis
  • beta Catenin / genetics*

Substances

  • MIRN515 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Long Noncoding
  • RNA, Neoplasm
  • Transcription Factors
  • ZFPM1 protein, human
  • beta Catenin