Hepatocellular carcinoma (HCC), as the most common type of liver cancer, is characterized by high recurrence and metastasis. Circular RNA (circRNA) circ_0036412 was selected for studying the underlying mechanisms of HCC.Quantitative real time-polymerase chain reaction (qRT-PCR) and western blot analyzed gene and protein expression. Functional experiments evaluated HCC cell proliferation, apoptosis and cell cycle in vitro. In vivo experiments detected HCC carcinogenesis in vivo. Fluorescence in situ hybridization (FISH) assays evaluated the subcellular distribution. Luciferase reporter, Chromatin immunoprecipitation (ChIP), DNA pulldown, RNA-binding protein immunoprecipitation (RIP), and RNA pulldown assays detected the underlying mechanisms.Circ_0036412 is overexpressed in HCC cells and features circular structure. PRDM1 activates circ_0036412 transcription to regulate the proliferation and cell cycle of HCC cells in vitro. Circ_0036412 modulates Hedgehog pathway. GLI2 propels HCC growth in vivo. Circ_0036412 up-regulates GLI2 expression by competitively binding to miR-579-3p, thus promoting the proliferation and inhibiting cell cycle arrest of HCC cells. Circ_0036412 stabilizes GLI2 expression by recruiting ELAVL1. Circ_0036412 propels the proliferation and inhibits cell cycle arrest of HCC cells in vitro through Hedgehog pathway.Circ_0036412 affects the proliferation and cell cycle of HCC via Hedgehog signaling pathway. It offers an insight into the targeted therapies of HCC. 

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

/pdf/circ-0036412-affects-the-proliferation-and-cell-cycle-of-2dkczpkw.pdf

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.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jcmm.16867

Jinlong Liu

Papers

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