NBPF4 mitigates progression in colorectal cancer through the regulation of EZH2‐associated ETFA. Issue 18 (18th August 2021)

• Record Type: Journal Article
• Authors: Chen, Wankun; Di, Zhou; Chen, Zhaoyuan; Nan, Ke; Gu, Jiahui; Ge, Feng; Liu, Jinlong; Zhang, Hao; Miao, Changhong
• Is Part Of: Journal of cellular and molecular medicine. Volume 25:Issue 18(2021)
• Page Start: 9038
• Page End: 9050
• Publication Date: 2021-08-18
• Subjects: colorectal cancer -- ETFA -- EZH2 -- NBPF4; Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.16867
• Languages: English
• ISSNs: 1582-1838

Abstract

Abstract: Colorectal cancer (CRC) is one of the leading causes of death worldwide, and hence, there is a need to elucidate the molecular mechanisms contributing to the progression of CRC. In this study, we aimed at assessing the role of long non‐coding RNA NBPF4 on the tumorigenesis of CRC. Silencing or overexpression experiments were performed on HCT116 and SW260 in vitro models. BALB/c athymic female nude mice aged 5–6 weeks were used as in vivo models. To assess the relationship between NBPF4 and its regulatory RNA pull‐down assay, RNA immunoprecipitation, luciferase activity, Western blotting and qRT‐PCR were employed. Initially, we identified that NBPF4 was downregulated in CRC tissues and cell lines. Furthermore, we observed that NBPF4 decreased tumorigenesis in both in vitro and in vivo models. Additionally, we identified that ETFA was highly expressed in CRCs and was negatively associated with NBPF4. Subsequently, we identified that EZH2, a transcriptional factor, activated ETFA by enhancing the methylation of its promoter, and EZH2 was also highly regulated in CRCs. Using COAD and READ databases, we confirmed that EZH2 and ETFA were positively correlated. Furthermore, we identified NBPF4 and EZH2 were targets for ZFP36, which bound and positively regulated NBPF4. This prevented NBPF4 from binding to its negative regulator miR‐17‐3p. Our results demonstrated that NBPF4 downregulated EZH2 and stabilized itself by binding to ZFP36, thus escaping from inhibition by miR‐17‐3p, which allowed mitigation of CRC through inhibition of ETFA.