Cargando…

Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a

BACKGROUND: Long noncoding RNA HULC is highly up-regulation in human hepatocellular carcinoma (HCC). However, the functions of HULC in hepatocarcinogenesis remains unclear. METHODS: RT-PCR, Western blotting, Chromatin immunoprecipitation (CHIP) assay, RNA Immunoprecipitation (RIP) and tumorignesis t...

Descripción completa

Detalles Bibliográficos
Autores principales: Xin, Xiaoru, Wu, Mengying, Meng, Qiuyu, Wang, Chen, Lu, Yanan, Yang, Yuxin, Li, Xiaonan, Zheng, Qidi, Pu, Hu, Gui, Xin, Li, Tianming, Li, Jiao, Jia, Song, Lu, Dongdong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5998602/
https://www.ncbi.nlm.nih.gov/pubmed/29895332
http://dx.doi.org/10.1186/s12943-018-0843-8
_version_ 1783331263372853248
author Xin, Xiaoru
Wu, Mengying
Meng, Qiuyu
Wang, Chen
Lu, Yanan
Yang, Yuxin
Li, Xiaonan
Zheng, Qidi
Pu, Hu
Gui, Xin
Li, Tianming
Li, Jiao
Jia, Song
Lu, Dongdong
author_facet Xin, Xiaoru
Wu, Mengying
Meng, Qiuyu
Wang, Chen
Lu, Yanan
Yang, Yuxin
Li, Xiaonan
Zheng, Qidi
Pu, Hu
Gui, Xin
Li, Tianming
Li, Jiao
Jia, Song
Lu, Dongdong
author_sort Xin, Xiaoru
collection PubMed
description BACKGROUND: Long noncoding RNA HULC is highly up-regulation in human hepatocellular carcinoma (HCC). However, the functions of HULC in hepatocarcinogenesis remains unclear. METHODS: RT-PCR, Western blotting, Chromatin immunoprecipitation (CHIP) assay, RNA Immunoprecipitation (RIP) and tumorignesis test in vitro and in vivo were performed. RESULTS: HULC is negatively associated with expression of PTEN or miR15a in patients of human liver cancer. Moreover, HULC accelerates malignant progression of liver cancer cells in vitro and in vivo. Mechanistically, HULC increasesthe expression of P62 via decreasing mature miR15a. On the other hand, excessive HULC increases the expression of LC3 on the level of transcription and then activates LC3 through Sirt1 (a deacetylase). Notably, HULC enhanced the interplay between LC3 and ATG3. Furthermore, HULC also increases the expression of becline-1(autophagy related gene). Therefore, HULC increases the cellular autophagy by increasing LC3II dependent on Sirt1.Noteworthy, excessive HULC reduces the expression of PTEN, β-catenin and enhances the expression of SAPK/JUNK, PKM2, CDK2, NOTCH1, C-Jun in liver cancer cells. Of significance, our observations also revealed that HULC inhibited PTEN through ubiquitin–proteasome system mediated by autophagy-P62.Ultimately,HULC activates AKT-PI3K-mTOR pathway through inhibiting PTEN in human liver cancer cells. CONCLUSIONS: This study elucidates a novel mechanism that lncRNA HULC produces a vital function during hepatocarcinogenesis.
format Online
Article
Text
id pubmed-5998602
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-59986022018-06-25 Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a Xin, Xiaoru Wu, Mengying Meng, Qiuyu Wang, Chen Lu, Yanan Yang, Yuxin Li, Xiaonan Zheng, Qidi Pu, Hu Gui, Xin Li, Tianming Li, Jiao Jia, Song Lu, Dongdong Mol Cancer Research BACKGROUND: Long noncoding RNA HULC is highly up-regulation in human hepatocellular carcinoma (HCC). However, the functions of HULC in hepatocarcinogenesis remains unclear. METHODS: RT-PCR, Western blotting, Chromatin immunoprecipitation (CHIP) assay, RNA Immunoprecipitation (RIP) and tumorignesis test in vitro and in vivo were performed. RESULTS: HULC is negatively associated with expression of PTEN or miR15a in patients of human liver cancer. Moreover, HULC accelerates malignant progression of liver cancer cells in vitro and in vivo. Mechanistically, HULC increasesthe expression of P62 via decreasing mature miR15a. On the other hand, excessive HULC increases the expression of LC3 on the level of transcription and then activates LC3 through Sirt1 (a deacetylase). Notably, HULC enhanced the interplay between LC3 and ATG3. Furthermore, HULC also increases the expression of becline-1(autophagy related gene). Therefore, HULC increases the cellular autophagy by increasing LC3II dependent on Sirt1.Noteworthy, excessive HULC reduces the expression of PTEN, β-catenin and enhances the expression of SAPK/JUNK, PKM2, CDK2, NOTCH1, C-Jun in liver cancer cells. Of significance, our observations also revealed that HULC inhibited PTEN through ubiquitin–proteasome system mediated by autophagy-P62.Ultimately,HULC activates AKT-PI3K-mTOR pathway through inhibiting PTEN in human liver cancer cells. CONCLUSIONS: This study elucidates a novel mechanism that lncRNA HULC produces a vital function during hepatocarcinogenesis. BioMed Central 2018-06-12 /pmc/articles/PMC5998602/ /pubmed/29895332 http://dx.doi.org/10.1186/s12943-018-0843-8 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Xin, Xiaoru
Wu, Mengying
Meng, Qiuyu
Wang, Chen
Lu, Yanan
Yang, Yuxin
Li, Xiaonan
Zheng, Qidi
Pu, Hu
Gui, Xin
Li, Tianming
Li, Jiao
Jia, Song
Lu, Dongdong
Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a
title Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a
title_full Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a
title_fullStr Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a
title_full_unstemmed Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a
title_short Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a
title_sort long noncoding rna hulc accelerates liver cancer by inhibiting pten via autophagy cooperation to mir15a
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5998602/
https://www.ncbi.nlm.nih.gov/pubmed/29895332
http://dx.doi.org/10.1186/s12943-018-0843-8
work_keys_str_mv AT xinxiaoru longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a
AT wumengying longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a
AT mengqiuyu longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a
AT wangchen longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a
AT luyanan longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a
AT yangyuxin longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a
AT lixiaonan longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a
AT zhengqidi longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a
AT puhu longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a
AT guixin longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a
AT litianming longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a
AT lijiao longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a
AT jiasong longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a
AT ludongdong longnoncodingrnahulcaccelerateslivercancerbyinhibitingptenviaautophagycooperationtomir15a