CircLIFR suppresses hepatocellular carcinoma progression by sponging miR-624-5p and inactivating the GSK-3β/β-catenin signaling pathway.

Abstract

Circular RNAs have been reported to play essential roles in the tumorigenesis and progression of various cancers. However, the biological processes and mechanisms involved in hepatocellular carcinoma (HCC) remain unclear. Initial RNA-sequencing data and qRT-PCR results in our cohort showed that hsa_circ_0072309 (also called circLIFR) was markedly downregulated in HCC tissues. Kaplan-Meier analysis indicated that higher levels of circLIFR in HCC patients correlated with favorable overall survival and recurrence-free survival rates. Both in vitro and in vivo experiments indicated that circLIFR inhibited the proliferation and invasion abilities of HCC cells. We therefore conducted related experiments to explore the mechanism of circLIFR in HCC. Fluorescence in situ hybridization results revealed that circLIFR was mainly located in the cytoplasm, and RNA immunoprecipitation assays indicated that circLIFR was significantly enriched by Ago2 protein. These results suggested that circLIFR may function as a sponge of miRNAs to regulate HCC progression. We further conducted bioinformatics prediction as well as dual-luciferase reporter assays, and the results of which showed that circLIFR could sponge miR-624-5p to stabilize glycogen synthase kinase 3β (GSK-3β) expression. Loss and gain of function experiments demonstrated that regulation of the expression of miR-624-5p or GSK-3β markedly affected HCC progression induced by circLIFR. Importantly, we also proved that circLIFR could facilitate the degradation of β-catenin and prevent its translocation to the nucleus in HCC cells. Overall, our study demonstrated that circLIFR acts as a tumor suppressor in HCC by regulating miR-624-5p and inactivating the GSK-3β/β-catenin signaling pathway.

• Authors: Lei Yang, Wenliang Tan, Yingcheng Wei, Zhiqin Xie, Wenxin Li, Xiaowu Ma, Qingbin Wang, Huilong Li, Ziyu Zhang, Changzhen Shang, Yajin Chen
• Journal: Cell death & disease (Cell Death Dis) Vol. 13 Issue 5 Pg. 464 (05 17 2022) ISSN: 2041-4889 [Electronic] England
• PMID: 35581180 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• MIRN624 microRNA, human
• MicroRNAs
• beta Catenin
• Glycogen Synthase Kinase 3 beta

Topics

• Carcinoma, Hepatocellular (pathology)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Gene Expression Regulation, Neoplastic (genetics)
• Glycogen Synthase Kinase 3 beta (genetics, metabolism)
• Humans
• In Situ Hybridization, Fluorescence
• Liver Neoplasms (pathology)
• MicroRNAs (genetics, metabolism)
• Signal Transduction
• beta Catenin (genetics, metabolism)