Cargando…

TP53-Activated lncRNA GHRLOS Regulates Cell Proliferation, Invasion, and Apoptosis of Non-Small Cell Lung Cancer by Modulating the miR-346/APC Axis

Non-small cell lung cancer (NSCLC) is the main type of lung cancer with high mortality worldwide. To improve NSCLC therapy, the exploration of molecular mechanisms involved in NSCLC progression and identification of their potential therapy targeting is important. Long noncoding RNAs (lncRNAs) have s...

Descripción completa

Detalles Bibliográficos
Autores principales: Ren, Ke, Sun, Jinghui, Liu, Lingling, Yang, Yuping, Li, Honghui, Wang, Zhichao, Deng, Jingzhu, Hou, Min, Qiu, Jia, Zhao, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097184/
https://www.ncbi.nlm.nih.gov/pubmed/33968785
http://dx.doi.org/10.3389/fonc.2021.676202
_version_ 1783688304974102528
author Ren, Ke
Sun, Jinghui
Liu, Lingling
Yang, Yuping
Li, Honghui
Wang, Zhichao
Deng, Jingzhu
Hou, Min
Qiu, Jia
Zhao, Wei
author_facet Ren, Ke
Sun, Jinghui
Liu, Lingling
Yang, Yuping
Li, Honghui
Wang, Zhichao
Deng, Jingzhu
Hou, Min
Qiu, Jia
Zhao, Wei
author_sort Ren, Ke
collection PubMed
description Non-small cell lung cancer (NSCLC) is the main type of lung cancer with high mortality worldwide. To improve NSCLC therapy, the exploration of molecular mechanisms involved in NSCLC progression and identification of their potential therapy targeting is important. Long noncoding RNAs (lncRNAs) have shown important roles in regulating various tumors progression, including NSCLC. We found lncRNA GHRLOS was decreased in NSCLC cell lines and tissues which correlated with poor prognosis of NSCLC patients. However, the role and underlying mechanisms of lncRNA GHRLOS in NSCLC progression remains elusive. The expression of lncRNA GHRLOS was examined in NSCLC cell lines and biopsy specimens of patients with NSCLC by quantitative real time polymerase chain reaction (qRT-PCR). The effects of GHRLOS on proliferation, invasion and apoptosis of NSCLC cells were determined by both in vitro and in vivo experiments. The interaction between GHRLOS and TP53 was determined by dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) combined with qRT-PCR analysis. RNA immunoprecipitation (RIP) was conducted to validate the binding between GHRLOS and microRNA-346 (miR-346). Dual-luciferase reporter assays were also carried out to reveal the interaction between miR-346 and the 3’ untranslated region (3’UTR) of adenomatous polyposis coli (APC) mRNA.Our data demonstrated that overexpression of lncRNA GHRLOS suppressed cancer cell proliferation and invasion as well as promoted cell apoptosis by regulating the expression of CDK2, PCNA, E-cadherin, N-cadherin, Bax, and Bcl-2 in NSCLC cells. Moreover, lncRNA GHRLOS was upregulated by the binding of TP53 to the GHRLOS promoter. The binding target of lncRNA GHRLOS was identified to be miR-346. Impressively, overexpression of miR-346 promoted cell proliferation and invasion, as well as inhibited cell apoptosis, however, these effects can be blocked by overexpression of lncRNA GHRLOS both in vitro and in vivo. In summary, this study reveals lncRNA GHRLOS, upregulated by TP53, acts as a molecule sponge of miR-346 to cooperatively modulates expression of APC, a miR-346 target, and potentially inhibits NSCLC progression via TP53/lncRNA GHRLOS/miR-346/APC axis, which represents a novel pathway that could be useful in targeted therapy against NSCLC.
format Online
Article
Text
id pubmed-8097184
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-80971842021-05-06 TP53-Activated lncRNA GHRLOS Regulates Cell Proliferation, Invasion, and Apoptosis of Non-Small Cell Lung Cancer by Modulating the miR-346/APC Axis Ren, Ke Sun, Jinghui Liu, Lingling Yang, Yuping Li, Honghui Wang, Zhichao Deng, Jingzhu Hou, Min Qiu, Jia Zhao, Wei Front Oncol Oncology Non-small cell lung cancer (NSCLC) is the main type of lung cancer with high mortality worldwide. To improve NSCLC therapy, the exploration of molecular mechanisms involved in NSCLC progression and identification of their potential therapy targeting is important. Long noncoding RNAs (lncRNAs) have shown important roles in regulating various tumors progression, including NSCLC. We found lncRNA GHRLOS was decreased in NSCLC cell lines and tissues which correlated with poor prognosis of NSCLC patients. However, the role and underlying mechanisms of lncRNA GHRLOS in NSCLC progression remains elusive. The expression of lncRNA GHRLOS was examined in NSCLC cell lines and biopsy specimens of patients with NSCLC by quantitative real time polymerase chain reaction (qRT-PCR). The effects of GHRLOS on proliferation, invasion and apoptosis of NSCLC cells were determined by both in vitro and in vivo experiments. The interaction between GHRLOS and TP53 was determined by dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) combined with qRT-PCR analysis. RNA immunoprecipitation (RIP) was conducted to validate the binding between GHRLOS and microRNA-346 (miR-346). Dual-luciferase reporter assays were also carried out to reveal the interaction between miR-346 and the 3’ untranslated region (3’UTR) of adenomatous polyposis coli (APC) mRNA.Our data demonstrated that overexpression of lncRNA GHRLOS suppressed cancer cell proliferation and invasion as well as promoted cell apoptosis by regulating the expression of CDK2, PCNA, E-cadherin, N-cadherin, Bax, and Bcl-2 in NSCLC cells. Moreover, lncRNA GHRLOS was upregulated by the binding of TP53 to the GHRLOS promoter. The binding target of lncRNA GHRLOS was identified to be miR-346. Impressively, overexpression of miR-346 promoted cell proliferation and invasion, as well as inhibited cell apoptosis, however, these effects can be blocked by overexpression of lncRNA GHRLOS both in vitro and in vivo. In summary, this study reveals lncRNA GHRLOS, upregulated by TP53, acts as a molecule sponge of miR-346 to cooperatively modulates expression of APC, a miR-346 target, and potentially inhibits NSCLC progression via TP53/lncRNA GHRLOS/miR-346/APC axis, which represents a novel pathway that could be useful in targeted therapy against NSCLC. Frontiers Media S.A. 2021-04-21 /pmc/articles/PMC8097184/ /pubmed/33968785 http://dx.doi.org/10.3389/fonc.2021.676202 Text en Copyright © 2021 Ren, Sun, Liu, Yang, Li, Wang, Deng, Hou, Qiu and Zhao 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 Oncology
Ren, Ke
Sun, Jinghui
Liu, Lingling
Yang, Yuping
Li, Honghui
Wang, Zhichao
Deng, Jingzhu
Hou, Min
Qiu, Jia
Zhao, Wei
TP53-Activated lncRNA GHRLOS Regulates Cell Proliferation, Invasion, and Apoptosis of Non-Small Cell Lung Cancer by Modulating the miR-346/APC Axis
title TP53-Activated lncRNA GHRLOS Regulates Cell Proliferation, Invasion, and Apoptosis of Non-Small Cell Lung Cancer by Modulating the miR-346/APC Axis
title_full TP53-Activated lncRNA GHRLOS Regulates Cell Proliferation, Invasion, and Apoptosis of Non-Small Cell Lung Cancer by Modulating the miR-346/APC Axis
title_fullStr TP53-Activated lncRNA GHRLOS Regulates Cell Proliferation, Invasion, and Apoptosis of Non-Small Cell Lung Cancer by Modulating the miR-346/APC Axis
title_full_unstemmed TP53-Activated lncRNA GHRLOS Regulates Cell Proliferation, Invasion, and Apoptosis of Non-Small Cell Lung Cancer by Modulating the miR-346/APC Axis
title_short TP53-Activated lncRNA GHRLOS Regulates Cell Proliferation, Invasion, and Apoptosis of Non-Small Cell Lung Cancer by Modulating the miR-346/APC Axis
title_sort tp53-activated lncrna ghrlos regulates cell proliferation, invasion, and apoptosis of non-small cell lung cancer by modulating the mir-346/apc axis
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097184/
https://www.ncbi.nlm.nih.gov/pubmed/33968785
http://dx.doi.org/10.3389/fonc.2021.676202
work_keys_str_mv AT renke tp53activatedlncrnaghrlosregulatescellproliferationinvasionandapoptosisofnonsmallcelllungcancerbymodulatingthemir346apcaxis
AT sunjinghui tp53activatedlncrnaghrlosregulatescellproliferationinvasionandapoptosisofnonsmallcelllungcancerbymodulatingthemir346apcaxis
AT liulingling tp53activatedlncrnaghrlosregulatescellproliferationinvasionandapoptosisofnonsmallcelllungcancerbymodulatingthemir346apcaxis
AT yangyuping tp53activatedlncrnaghrlosregulatescellproliferationinvasionandapoptosisofnonsmallcelllungcancerbymodulatingthemir346apcaxis
AT lihonghui tp53activatedlncrnaghrlosregulatescellproliferationinvasionandapoptosisofnonsmallcelllungcancerbymodulatingthemir346apcaxis
AT wangzhichao tp53activatedlncrnaghrlosregulatescellproliferationinvasionandapoptosisofnonsmallcelllungcancerbymodulatingthemir346apcaxis
AT dengjingzhu tp53activatedlncrnaghrlosregulatescellproliferationinvasionandapoptosisofnonsmallcelllungcancerbymodulatingthemir346apcaxis
AT houmin tp53activatedlncrnaghrlosregulatescellproliferationinvasionandapoptosisofnonsmallcelllungcancerbymodulatingthemir346apcaxis
AT qiujia tp53activatedlncrnaghrlosregulatescellproliferationinvasionandapoptosisofnonsmallcelllungcancerbymodulatingthemir346apcaxis
AT zhaowei tp53activatedlncrnaghrlosregulatescellproliferationinvasionandapoptosisofnonsmallcelllungcancerbymodulatingthemir346apcaxis