NBPF4 mitigates progression in colorectal cancer through the regulation of EZH2‐associated ETFA

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.

MiR-934 Exacerbates Malignancy of Gastric Cancer Cells by Targeting ZFP36

“…Except for acting as target gene, ZFP36 could also bind to RNAs to impact the cellular functions of tumor cells. ZFP36 stabilized NBPF4 via the binding relationship, thus assisting NBPF4 to escape from inhibition by miR-17-3p, which ameliorated colorectal cancer ( 35 ). In our present study, we proved that the protein level of ZFP36 was downregulated in GC tissues, which was in accordant with the previous studies ( 36 , 37 ).…”

Circ_0036412 affects the proliferation and cell cycle of hepatocellular carcinoma via hedgehog signaling pathway

“…The host gene of circ_0036412, ETFA has been reported to be associated with Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) [ 14 ]. Moreover, NBPF4 regulates ETFA, which is associated with EZH2, to attenuate the progression of colorectal cancer [ 15 ].…”