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

Abstract

Abstract Background 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. Methods 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. Results 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. Conclusions Circ_0036412 affects the proliferation and cell cycle of HCC via Hedgehog signaling pathway. It offers an insight into the targeted therapies of HCC. Graphical Abstract