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

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. Conclusions 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.

Identification of HOXA1 as a Novel Biomarker in Prognosis of Head and Neck Squamous Cell Carcinoma

“…The expression of HOXA1 is tissue-specific (Fagerberg et al, 2014 ) ( https://www.proteinatlas.org ), and as tumor modulators, it may cover a wide range of functionality in types of tumor dependent on the cellular context (Shah and Sukumar, 2010 ). HOXA1 played a role of an oncogene in breast carcinoma (Liu et al, 2019 ), lung carcinoma (Abe et al, 2006 ), oral squamous cell carcinoma (Bitu et al, 2012 ), hepatocellular carcinoma (Zha et al, 2012 ), melanoma (Wardwell-Ozgo et al, 2014 ), gastric cancer (Yuan et al, 2016 ), leukemia (Chen et al, 2019 ) and retinoblastoma (RB) (Lyv et al, 2020 ). Inversely, it is shown as anti-oncogenes in pancreatic carcinoma (Ohuchida et al, 2012 ) and small cell lung cancer (SCLC) (Xiao et al, 2014 ).…”

ZFPM2-AS1 transcriptionally mediated by STAT1 regulates thyroid cancer cell growth, migration and invasion via miR-515-5p/TUSC3

“…ZFPM2-AS1 promotes the growth of esophageal squamous cell carcinoma cells by up-regulation of TRAF4 and NF-κB [12]. Silencing ZFPM2-AS1 weakens retinoblastoma progression through mediating miR-515/HOXA1 axis [13]. Nevertheless, its roles in thyroid cancer are still undiscovered.…”

ZFPM2‐AS1 facilitates cell proliferation and migration in cutaneous malignant melanoma through modulating miR‐650/NOTCH1 signaling

“…It has been documented that ZFPM2‐AS1 promotes the development of retinoblastoma by activating the Wnt/β‐catenin signaling pathway 16 . Thus we supposed that ZFPM2‐AS1 might facilitate the progression of cutaneous melanoma via regulating some certain signaling pathway.…”