Cargando…

METTL16 promotes hepatocellular carcinoma progression through downregulating RAB11B-AS1 in an m(6)A-dependent manner

BACKGROUND: The molecular mechanisms driving hepatocellular carcinoma (HCC) remain largely unclear. As one of the major epitranscriptomic modifications, N(6)-methyladenosine (m(6)A) plays key roles in HCC. The aim of this study was to investigate the expression, roles, and mechanisms of action of th...

Descripción completa

Detalles Bibliográficos
Autores principales: Dai, Yun-zhang, Liu, Yong-da, Li, Jie, Chen, Mei-ting, Huang, Mei, Wang, Fang, Yang, Qing-song, Yuan, Ji-hang, Sun, Shu-han
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9123709/
https://www.ncbi.nlm.nih.gov/pubmed/35596159
http://dx.doi.org/10.1186/s11658-022-00342-8
_version_ 1784711608397725696
author Dai, Yun-zhang
Liu, Yong-da
Li, Jie
Chen, Mei-ting
Huang, Mei
Wang, Fang
Yang, Qing-song
Yuan, Ji-hang
Sun, Shu-han
author_facet Dai, Yun-zhang
Liu, Yong-da
Li, Jie
Chen, Mei-ting
Huang, Mei
Wang, Fang
Yang, Qing-song
Yuan, Ji-hang
Sun, Shu-han
author_sort Dai, Yun-zhang
collection PubMed
description BACKGROUND: The molecular mechanisms driving hepatocellular carcinoma (HCC) remain largely unclear. As one of the major epitranscriptomic modifications, N(6)-methyladenosine (m(6)A) plays key roles in HCC. The aim of this study was to investigate the expression, roles, and mechanisms of action of the RNA methyltransferase methyltransferase-like protein 16 (METTL16) in HCC. METHODS: The expression of METTL16 and RAB11B-AS1 was determined by RT-qPCR. The regulation of RAB11B-AS1 by METTL16 was investigated by RNA immunoprecipitation (RIP), methylated RIP (MeRIP), and RNA stability assays. In vitro and in vivo gain- and loss-of-function assays were performed to investigate the roles of METTL16 and RAB11B-AS1. RESULTS: METTL16 was upregulated in HCC, and its increased expression was correlated with poor prognosis of HCC patients. METTL16 promoted HCC cellular proliferation, migration, and invasion, repressed HCC cellular apoptosis, and promoted HCC tumoral growth in vivo. METTL16 directly bound long noncoding RNA (lncRNA) RAB11B-AS1, induced m(6)A modification of RAB11B-AS1, and decreased the stability of RAB11B-AS1 transcript, leading to the downregulation of RAB11B-AS1. Conversely to METTL16, RAB11B-AS1 is downregulated in HCC, and its decreased expression was correlated with poor prognosis of patients with HCC. Furthermore, the expression of RAB11B-AS1 was negatively correlated with METTL16 in HCC tissues. RAB11B-AS1 repressed HCC cellular proliferation, migration, and invasion, promoted HCC cellular apoptosis, and inhibited HCC tumoral growth in vivo. Functional rescue assays revealed that overexpression of RAB11B-AS1 reversed the oncogenic roles of METTL16 in HCC. CONCLUSIONS: This study identified the METTL16/RAB11B-AS1 regulatory axis in HCC, which represented novel targets for HCC prognosis and treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11658-022-00342-8.
format Online
Article
Text
id pubmed-9123709
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-91237092022-05-22 METTL16 promotes hepatocellular carcinoma progression through downregulating RAB11B-AS1 in an m(6)A-dependent manner Dai, Yun-zhang Liu, Yong-da Li, Jie Chen, Mei-ting Huang, Mei Wang, Fang Yang, Qing-song Yuan, Ji-hang Sun, Shu-han Cell Mol Biol Lett Research BACKGROUND: The molecular mechanisms driving hepatocellular carcinoma (HCC) remain largely unclear. As one of the major epitranscriptomic modifications, N(6)-methyladenosine (m(6)A) plays key roles in HCC. The aim of this study was to investigate the expression, roles, and mechanisms of action of the RNA methyltransferase methyltransferase-like protein 16 (METTL16) in HCC. METHODS: The expression of METTL16 and RAB11B-AS1 was determined by RT-qPCR. The regulation of RAB11B-AS1 by METTL16 was investigated by RNA immunoprecipitation (RIP), methylated RIP (MeRIP), and RNA stability assays. In vitro and in vivo gain- and loss-of-function assays were performed to investigate the roles of METTL16 and RAB11B-AS1. RESULTS: METTL16 was upregulated in HCC, and its increased expression was correlated with poor prognosis of HCC patients. METTL16 promoted HCC cellular proliferation, migration, and invasion, repressed HCC cellular apoptosis, and promoted HCC tumoral growth in vivo. METTL16 directly bound long noncoding RNA (lncRNA) RAB11B-AS1, induced m(6)A modification of RAB11B-AS1, and decreased the stability of RAB11B-AS1 transcript, leading to the downregulation of RAB11B-AS1. Conversely to METTL16, RAB11B-AS1 is downregulated in HCC, and its decreased expression was correlated with poor prognosis of patients with HCC. Furthermore, the expression of RAB11B-AS1 was negatively correlated with METTL16 in HCC tissues. RAB11B-AS1 repressed HCC cellular proliferation, migration, and invasion, promoted HCC cellular apoptosis, and inhibited HCC tumoral growth in vivo. Functional rescue assays revealed that overexpression of RAB11B-AS1 reversed the oncogenic roles of METTL16 in HCC. CONCLUSIONS: This study identified the METTL16/RAB11B-AS1 regulatory axis in HCC, which represented novel targets for HCC prognosis and treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11658-022-00342-8. BioMed Central 2022-05-20 /pmc/articles/PMC9123709/ /pubmed/35596159 http://dx.doi.org/10.1186/s11658-022-00342-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research
Dai, Yun-zhang
Liu, Yong-da
Li, Jie
Chen, Mei-ting
Huang, Mei
Wang, Fang
Yang, Qing-song
Yuan, Ji-hang
Sun, Shu-han
METTL16 promotes hepatocellular carcinoma progression through downregulating RAB11B-AS1 in an m(6)A-dependent manner
title METTL16 promotes hepatocellular carcinoma progression through downregulating RAB11B-AS1 in an m(6)A-dependent manner
title_full METTL16 promotes hepatocellular carcinoma progression through downregulating RAB11B-AS1 in an m(6)A-dependent manner
title_fullStr METTL16 promotes hepatocellular carcinoma progression through downregulating RAB11B-AS1 in an m(6)A-dependent manner
title_full_unstemmed METTL16 promotes hepatocellular carcinoma progression through downregulating RAB11B-AS1 in an m(6)A-dependent manner
title_short METTL16 promotes hepatocellular carcinoma progression through downregulating RAB11B-AS1 in an m(6)A-dependent manner
title_sort mettl16 promotes hepatocellular carcinoma progression through downregulating rab11b-as1 in an m(6)a-dependent manner
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9123709/
https://www.ncbi.nlm.nih.gov/pubmed/35596159
http://dx.doi.org/10.1186/s11658-022-00342-8
work_keys_str_mv AT daiyunzhang mettl16promoteshepatocellularcarcinomaprogressionthroughdownregulatingrab11bas1inanm6adependentmanner
AT liuyongda mettl16promoteshepatocellularcarcinomaprogressionthroughdownregulatingrab11bas1inanm6adependentmanner
AT lijie mettl16promoteshepatocellularcarcinomaprogressionthroughdownregulatingrab11bas1inanm6adependentmanner
AT chenmeiting mettl16promoteshepatocellularcarcinomaprogressionthroughdownregulatingrab11bas1inanm6adependentmanner
AT huangmei mettl16promoteshepatocellularcarcinomaprogressionthroughdownregulatingrab11bas1inanm6adependentmanner
AT wangfang mettl16promoteshepatocellularcarcinomaprogressionthroughdownregulatingrab11bas1inanm6adependentmanner
AT yangqingsong mettl16promoteshepatocellularcarcinomaprogressionthroughdownregulatingrab11bas1inanm6adependentmanner
AT yuanjihang mettl16promoteshepatocellularcarcinomaprogressionthroughdownregulatingrab11bas1inanm6adependentmanner
AT sunshuhan mettl16promoteshepatocellularcarcinomaprogressionthroughdownregulatingrab11bas1inanm6adependentmanner