Cargando…

Long noncoding RNA SNHG16 induces sorafenib resistance in hepatocellular carcinoma cells through sponging miR-140-5p

BACKGROUND: Sorafenib is widely used for treatment of hepatocellular carcinoma (HCC), but the acquired resistance remains a major obstacle for its application. Thus it is of critical importance to elucidate the molecular mechanisms underlying sorafenib resistance in HCC. This study aimed to determin...

Descripción completa

Detalles Bibliográficos
Autores principales: Ye, Junfeng, Zhang, Ruoyan, Du, Xiaohong, Chai, Wengang, Zhou, Qiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324603/
https://www.ncbi.nlm.nih.gov/pubmed/30655679
http://dx.doi.org/10.2147/OTT.S175176
_version_ 1783386002578997248
author Ye, Junfeng
Zhang, Ruoyan
Du, Xiaohong
Chai, Wengang
Zhou, Qiang
author_facet Ye, Junfeng
Zhang, Ruoyan
Du, Xiaohong
Chai, Wengang
Zhou, Qiang
author_sort Ye, Junfeng
collection PubMed
description BACKGROUND: Sorafenib is widely used for treatment of hepatocellular carcinoma (HCC), but the acquired resistance remains a major obstacle for its application. Thus it is of critical importance to elucidate the molecular mechanisms underlying sorafenib resistance in HCC. This study aimed to determine the roles of long noncoding RNA SNHG16 in sorafenib-resistant HCC cells. METHODS: HCC and matched adjacent normal liver tissue samples were obtained from 103 HCC patients. Sorafenib-resistant HepG2/SOR cell line was established from its parental HepG2 cells by exposure to increasing concentrations of sorafenib. SNHG16 and miR-140-5p expression levels in tissue samples and cells were detected by RT-qPCR analysis. The sensitivity of cells to sorafenib in vitro was evaluated by MTT assay, and the sensitivity of HepG2/SOR cells to sorafenib in vivo was estimated using the nude mouse-based xenograft model. The potential binding relation between SNHG16 and miR-140-5p was validated by dual luciferase reporter assay and biotinylated RNA pull-down assay. RESULTS: The results showed that SNHG16 expression was remarkably increased in HCC tissues and cell lines, and its high expression was closely associated with aggressive clinicopathological features and poor prognosis of HCC patients. Further experiments showed that SNHG16 is upregulated in HepG2/SOR cells, whereas knockdown of SNHG16 increases the sensitivity of HepG2/SOR cells to sorafenib in vitro and in vivo. Further mechanistic study identified that SNHG16 functions as an endogenous sponge for miR-140-5p in HepG2 cells, and in HCC tissues, the expression of miR-140-5p is negatively correlated with SNHG16 expression. Moreover, miR-140-5p overexpression also increases the sensitivity of HepG2/SOR cells to sorafenib, and the effects of SNHG16 knockdown on sorafenib resistance could be blocked by miR-140-5p inhibitor. CONCLUSION: Collectively, our findings demonstrated that knockdown of SNHG16 attenuated sorafenib resistance in HCC through sponging miR-140-5p, indicating that SNHG16 might be as a promising therapeutic target to boost the effectiveness of chemotherapy for HCC patients.
format Online
Article
Text
id pubmed-6324603
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Dove Medical Press
record_format MEDLINE/PubMed
spelling pubmed-63246032019-01-17 Long noncoding RNA SNHG16 induces sorafenib resistance in hepatocellular carcinoma cells through sponging miR-140-5p Ye, Junfeng Zhang, Ruoyan Du, Xiaohong Chai, Wengang Zhou, Qiang Onco Targets Ther Original Research BACKGROUND: Sorafenib is widely used for treatment of hepatocellular carcinoma (HCC), but the acquired resistance remains a major obstacle for its application. Thus it is of critical importance to elucidate the molecular mechanisms underlying sorafenib resistance in HCC. This study aimed to determine the roles of long noncoding RNA SNHG16 in sorafenib-resistant HCC cells. METHODS: HCC and matched adjacent normal liver tissue samples were obtained from 103 HCC patients. Sorafenib-resistant HepG2/SOR cell line was established from its parental HepG2 cells by exposure to increasing concentrations of sorafenib. SNHG16 and miR-140-5p expression levels in tissue samples and cells were detected by RT-qPCR analysis. The sensitivity of cells to sorafenib in vitro was evaluated by MTT assay, and the sensitivity of HepG2/SOR cells to sorafenib in vivo was estimated using the nude mouse-based xenograft model. The potential binding relation between SNHG16 and miR-140-5p was validated by dual luciferase reporter assay and biotinylated RNA pull-down assay. RESULTS: The results showed that SNHG16 expression was remarkably increased in HCC tissues and cell lines, and its high expression was closely associated with aggressive clinicopathological features and poor prognosis of HCC patients. Further experiments showed that SNHG16 is upregulated in HepG2/SOR cells, whereas knockdown of SNHG16 increases the sensitivity of HepG2/SOR cells to sorafenib in vitro and in vivo. Further mechanistic study identified that SNHG16 functions as an endogenous sponge for miR-140-5p in HepG2 cells, and in HCC tissues, the expression of miR-140-5p is negatively correlated with SNHG16 expression. Moreover, miR-140-5p overexpression also increases the sensitivity of HepG2/SOR cells to sorafenib, and the effects of SNHG16 knockdown on sorafenib resistance could be blocked by miR-140-5p inhibitor. CONCLUSION: Collectively, our findings demonstrated that knockdown of SNHG16 attenuated sorafenib resistance in HCC through sponging miR-140-5p, indicating that SNHG16 might be as a promising therapeutic target to boost the effectiveness of chemotherapy for HCC patients. Dove Medical Press 2019-01-04 /pmc/articles/PMC6324603/ /pubmed/30655679 http://dx.doi.org/10.2147/OTT.S175176 Text en © 2019 Ye et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Ye, Junfeng
Zhang, Ruoyan
Du, Xiaohong
Chai, Wengang
Zhou, Qiang
Long noncoding RNA SNHG16 induces sorafenib resistance in hepatocellular carcinoma cells through sponging miR-140-5p
title Long noncoding RNA SNHG16 induces sorafenib resistance in hepatocellular carcinoma cells through sponging miR-140-5p
title_full Long noncoding RNA SNHG16 induces sorafenib resistance in hepatocellular carcinoma cells through sponging miR-140-5p
title_fullStr Long noncoding RNA SNHG16 induces sorafenib resistance in hepatocellular carcinoma cells through sponging miR-140-5p
title_full_unstemmed Long noncoding RNA SNHG16 induces sorafenib resistance in hepatocellular carcinoma cells through sponging miR-140-5p
title_short Long noncoding RNA SNHG16 induces sorafenib resistance in hepatocellular carcinoma cells through sponging miR-140-5p
title_sort long noncoding rna snhg16 induces sorafenib resistance in hepatocellular carcinoma cells through sponging mir-140-5p
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324603/
https://www.ncbi.nlm.nih.gov/pubmed/30655679
http://dx.doi.org/10.2147/OTT.S175176
work_keys_str_mv AT yejunfeng longnoncodingrnasnhg16inducessorafenibresistanceinhepatocellularcarcinomacellsthroughspongingmir1405p
AT zhangruoyan longnoncodingrnasnhg16inducessorafenibresistanceinhepatocellularcarcinomacellsthroughspongingmir1405p
AT duxiaohong longnoncodingrnasnhg16inducessorafenibresistanceinhepatocellularcarcinomacellsthroughspongingmir1405p
AT chaiwengang longnoncodingrnasnhg16inducessorafenibresistanceinhepatocellularcarcinomacellsthroughspongingmir1405p
AT zhouqiang longnoncodingrnasnhg16inducessorafenibresistanceinhepatocellularcarcinomacellsthroughspongingmir1405p