Cargando…

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

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_...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Lei, Tan, Wenliang, Wei, Yingcheng, Xie, Zhiqin, Li, Wenxin, Ma, Xiaowu, Wang, Qingbin, Li, Huilong, Zhang, Ziyu, Shang, Changzhen, Chen, Yajin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114368/
https://www.ncbi.nlm.nih.gov/pubmed/35581180
http://dx.doi.org/10.1038/s41419-022-04887-6
_version_ 1784709757176643584
author Yang, Lei
Tan, Wenliang
Wei, Yingcheng
Xie, Zhiqin
Li, Wenxin
Ma, Xiaowu
Wang, Qingbin
Li, Huilong
Zhang, Ziyu
Shang, Changzhen
Chen, Yajin
author_facet Yang, Lei
Tan, Wenliang
Wei, Yingcheng
Xie, Zhiqin
Li, Wenxin
Ma, Xiaowu
Wang, Qingbin
Li, Huilong
Zhang, Ziyu
Shang, Changzhen
Chen, Yajin
author_sort Yang, Lei
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9114368
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-91143682022-05-19 CircLIFR suppresses hepatocellular carcinoma progression by sponging miR-624-5p and inactivating the GSK-3β/β-catenin signaling pathway Yang, Lei Tan, Wenliang Wei, Yingcheng Xie, Zhiqin Li, Wenxin Ma, Xiaowu Wang, Qingbin Li, Huilong Zhang, Ziyu Shang, Changzhen Chen, Yajin Cell Death Dis Article 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. Nature Publishing Group UK 2022-05-17 /pmc/articles/PMC9114368/ /pubmed/35581180 http://dx.doi.org/10.1038/s41419-022-04887-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Yang, Lei
Tan, Wenliang
Wei, Yingcheng
Xie, Zhiqin
Li, Wenxin
Ma, Xiaowu
Wang, Qingbin
Li, Huilong
Zhang, Ziyu
Shang, Changzhen
Chen, Yajin
CircLIFR suppresses hepatocellular carcinoma progression by sponging miR-624-5p and inactivating the GSK-3β/β-catenin signaling pathway
title CircLIFR suppresses hepatocellular carcinoma progression by sponging miR-624-5p and inactivating the GSK-3β/β-catenin signaling pathway
title_full CircLIFR suppresses hepatocellular carcinoma progression by sponging miR-624-5p and inactivating the GSK-3β/β-catenin signaling pathway
title_fullStr CircLIFR suppresses hepatocellular carcinoma progression by sponging miR-624-5p and inactivating the GSK-3β/β-catenin signaling pathway
title_full_unstemmed CircLIFR suppresses hepatocellular carcinoma progression by sponging miR-624-5p and inactivating the GSK-3β/β-catenin signaling pathway
title_short CircLIFR suppresses hepatocellular carcinoma progression by sponging miR-624-5p and inactivating the GSK-3β/β-catenin signaling pathway
title_sort circlifr suppresses hepatocellular carcinoma progression by sponging mir-624-5p and inactivating the gsk-3β/β-catenin signaling pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114368/
https://www.ncbi.nlm.nih.gov/pubmed/35581180
http://dx.doi.org/10.1038/s41419-022-04887-6
work_keys_str_mv AT yanglei circlifrsuppresseshepatocellularcarcinomaprogressionbyspongingmir6245pandinactivatingthegsk3bbcateninsignalingpathway
AT tanwenliang circlifrsuppresseshepatocellularcarcinomaprogressionbyspongingmir6245pandinactivatingthegsk3bbcateninsignalingpathway
AT weiyingcheng circlifrsuppresseshepatocellularcarcinomaprogressionbyspongingmir6245pandinactivatingthegsk3bbcateninsignalingpathway
AT xiezhiqin circlifrsuppresseshepatocellularcarcinomaprogressionbyspongingmir6245pandinactivatingthegsk3bbcateninsignalingpathway
AT liwenxin circlifrsuppresseshepatocellularcarcinomaprogressionbyspongingmir6245pandinactivatingthegsk3bbcateninsignalingpathway
AT maxiaowu circlifrsuppresseshepatocellularcarcinomaprogressionbyspongingmir6245pandinactivatingthegsk3bbcateninsignalingpathway
AT wangqingbin circlifrsuppresseshepatocellularcarcinomaprogressionbyspongingmir6245pandinactivatingthegsk3bbcateninsignalingpathway
AT lihuilong circlifrsuppresseshepatocellularcarcinomaprogressionbyspongingmir6245pandinactivatingthegsk3bbcateninsignalingpathway
AT zhangziyu circlifrsuppresseshepatocellularcarcinomaprogressionbyspongingmir6245pandinactivatingthegsk3bbcateninsignalingpathway
AT shangchangzhen circlifrsuppresseshepatocellularcarcinomaprogressionbyspongingmir6245pandinactivatingthegsk3bbcateninsignalingpathway
AT chenyajin circlifrsuppresseshepatocellularcarcinomaprogressionbyspongingmir6245pandinactivatingthegsk3bbcateninsignalingpathway