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Downregulation of circLIFR exerts cancer-promoting effects on hepatocellular carcinoma in vitro

Hepatocellular carcinoma (HCC) is one of the most fatal malignant tumors worldwide. Circular RNAs (circRNAs) are a special type of RNA that lacks the 5′ and 3’ ends. The functional roles of circRNAs in HCC remain largely unknown. Using high-throughput sequencing, we found several differentially expr...

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Autores principales: Ji, Jingzhang, Tang, Jialyu, Ren, Ping, Cai, Wenpin, Shen, Meina, Wang, Qiunan, Yang, Xiaoyun, Chen, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9513674/
https://www.ncbi.nlm.nih.gov/pubmed/36176304
http://dx.doi.org/10.3389/fgene.2022.986322
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author Ji, Jingzhang
Tang, Jialyu
Ren, Ping
Cai, Wenpin
Shen, Meina
Wang, Qiunan
Yang, Xiaoyun
Chen, Wei
author_facet Ji, Jingzhang
Tang, Jialyu
Ren, Ping
Cai, Wenpin
Shen, Meina
Wang, Qiunan
Yang, Xiaoyun
Chen, Wei
author_sort Ji, Jingzhang
collection PubMed
description Hepatocellular carcinoma (HCC) is one of the most fatal malignant tumors worldwide. Circular RNAs (circRNAs) are a special type of RNA that lacks the 5′ and 3’ ends. The functional roles of circRNAs in HCC remain largely unknown. Using high-throughput sequencing, we found several differentially expressed circRNAs in HCC tissues compared with nearby normal tissues. Among them, circRNA derived from the LIFR gene, named circLIFR, was significantly downregulated in HCC. Intriguingly, circLIFR overexpression in SK-Hep-1 cells promoted cell growth and invasion. RNA pull-down and mass spectrometry detection revealed circLIFR interacting with TANK binding kinase 1 (TBK1). Anti-TBK1 RIP confirmed the interaction between circLIFR and TBK1. TBK1 is a serine/threonine kinase that regulates several signaling pathways, including the NF-κB pathway. TBK1 inhibitors inhibit NF-κB activation. Overexpression of circLIFR overcame the in-hibitory function of TBK1, resulting in the upregulation of several genes, including MMP13, MMP3, VEGF, and MAPK. This study shows that the downregulation of circLIFR in HCC has a can-cer-promoting effect by interacting with TBK1 to promote the activation of downstream NF-κB pathway genes related to cell proliferation, migration, and invasion. This novel finding reveals the diversity of circRNA functions in HCC and provides novel insights into the role of circRNAs.
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spelling pubmed-95136742022-09-28 Downregulation of circLIFR exerts cancer-promoting effects on hepatocellular carcinoma in vitro Ji, Jingzhang Tang, Jialyu Ren, Ping Cai, Wenpin Shen, Meina Wang, Qiunan Yang, Xiaoyun Chen, Wei Front Genet Genetics Hepatocellular carcinoma (HCC) is one of the most fatal malignant tumors worldwide. Circular RNAs (circRNAs) are a special type of RNA that lacks the 5′ and 3’ ends. The functional roles of circRNAs in HCC remain largely unknown. Using high-throughput sequencing, we found several differentially expressed circRNAs in HCC tissues compared with nearby normal tissues. Among them, circRNA derived from the LIFR gene, named circLIFR, was significantly downregulated in HCC. Intriguingly, circLIFR overexpression in SK-Hep-1 cells promoted cell growth and invasion. RNA pull-down and mass spectrometry detection revealed circLIFR interacting with TANK binding kinase 1 (TBK1). Anti-TBK1 RIP confirmed the interaction between circLIFR and TBK1. TBK1 is a serine/threonine kinase that regulates several signaling pathways, including the NF-κB pathway. TBK1 inhibitors inhibit NF-κB activation. Overexpression of circLIFR overcame the in-hibitory function of TBK1, resulting in the upregulation of several genes, including MMP13, MMP3, VEGF, and MAPK. This study shows that the downregulation of circLIFR in HCC has a can-cer-promoting effect by interacting with TBK1 to promote the activation of downstream NF-κB pathway genes related to cell proliferation, migration, and invasion. This novel finding reveals the diversity of circRNA functions in HCC and provides novel insights into the role of circRNAs. Frontiers Media S.A. 2022-09-12 /pmc/articles/PMC9513674/ /pubmed/36176304 http://dx.doi.org/10.3389/fgene.2022.986322 Text en Copyright © 2022 Ji, Tang, Ren, Cai, Shen, Wang, Yang and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Ji, Jingzhang
Tang, Jialyu
Ren, Ping
Cai, Wenpin
Shen, Meina
Wang, Qiunan
Yang, Xiaoyun
Chen, Wei
Downregulation of circLIFR exerts cancer-promoting effects on hepatocellular carcinoma in vitro
title Downregulation of circLIFR exerts cancer-promoting effects on hepatocellular carcinoma in vitro
title_full Downregulation of circLIFR exerts cancer-promoting effects on hepatocellular carcinoma in vitro
title_fullStr Downregulation of circLIFR exerts cancer-promoting effects on hepatocellular carcinoma in vitro
title_full_unstemmed Downregulation of circLIFR exerts cancer-promoting effects on hepatocellular carcinoma in vitro
title_short Downregulation of circLIFR exerts cancer-promoting effects on hepatocellular carcinoma in vitro
title_sort downregulation of circlifr exerts cancer-promoting effects on hepatocellular carcinoma in vitro
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9513674/
https://www.ncbi.nlm.nih.gov/pubmed/36176304
http://dx.doi.org/10.3389/fgene.2022.986322
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