Long Non-Coding RNA THOR Depletion Inhibits Human Non-Small Cell Lung Cancer Cell Growth

Long non-coding RNA (LncRNA) THOR (Lnc-THOR) is expressed in testis and multiple human malignancies. Lnc-THOR association with IGF2BP1 (IGF2 mRNA-binding protein 1) is essential for stabilization and transcription of IGF2BP1 targeted mRNAs. We tested its expression and potential functions in non-sma...

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Autores principales:	Peng-Fei Jiao, Pei-jun Tang, Dan Chu, Ya-meng Li, Wei-hua Xu, Gao-Fei Ren
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	NSCLC Lnc-THOR IGF2BP1 cell growth signaling Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/5e82f97a570f4966933e7f7adbcf7bee
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spelling	oai:doaj.org-article:5e82f97a570f4966933e7f7adbcf7bee2021-11-17T05:07:11ZLong Non-Coding RNA THOR Depletion Inhibits Human Non-Small Cell Lung Cancer Cell Growth2234-943X10.3389/fonc.2021.756148https://doaj.org/article/5e82f97a570f4966933e7f7adbcf7bee2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.756148/fullhttps://doaj.org/toc/2234-943XLong non-coding RNA (LncRNA) THOR (Lnc-THOR) is expressed in testis and multiple human malignancies. Lnc-THOR association with IGF2BP1 (IGF2 mRNA-binding protein 1) is essential for stabilization and transcription of IGF2BP1 targeted mRNAs. We tested its expression and potential functions in non-small cell lung cancer (NSCLC). In primary NSCLC cells and established cell lines, Lnc-THOR shRNA or CRISPR/Cas9-mediated knockout (KO) downregulated IGF2BP1 target mRNAs (IGF2, Gli1, Myc and SOX9), inhibiting cell viability, growth, proliferation, migration and invasion. Significant apoptosis activation was detected in Lnc-THOR-silenced/-KO NSCLC cells. Conversely, ectopic overexpression of Lnc-THOR upregulated IGF2BP1 mRNA targets and enhanced NSCLC cell proliferation, migration and invasion. RNA-immunoprecipitation and RNA pull-down assay results confirmed the direct binding between Lnc-THOR and IGF2BP1 protein in NSCLC cells. Lnc-THOR silencing and overexpression were ineffective in IGF2BP1-KO NSCLC cells. Forced IGF2BP1 overexpression failed to rescue Lnc-THOR-KO NSCLC cells. In vivo, intratumoral injection of Lnc-THOR shRNA adeno-associated virus potently inhibited A549 xenograft tumor growth in nude mice. At last we show that Lnc-THOR is overexpressed in multiple NSCLC tissues and established/primary NSCLC cells. Collectively, these results highlighted the ability of Lnc-THOR in promoting NSCLC cell growth by associating with IGF2BP1, suggesting that Lnc-THOR represents a promising therapeutic target of NSCLC.Peng-Fei JiaoPei-jun TangDan ChuYa-meng LiWei-hua XuGao-Fei RenFrontiers Media S.A.articleNSCLCLnc-THORIGF2BP1cell growthsignalingNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	NSCLC Lnc-THOR IGF2BP1 cell growth signaling Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	NSCLC Lnc-THOR IGF2BP1 cell growth signaling Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Peng-Fei Jiao Pei-jun Tang Dan Chu Ya-meng Li Wei-hua Xu Gao-Fei Ren Long Non-Coding RNA THOR Depletion Inhibits Human Non-Small Cell Lung Cancer Cell Growth
description	Long non-coding RNA (LncRNA) THOR (Lnc-THOR) is expressed in testis and multiple human malignancies. Lnc-THOR association with IGF2BP1 (IGF2 mRNA-binding protein 1) is essential for stabilization and transcription of IGF2BP1 targeted mRNAs. We tested its expression and potential functions in non-small cell lung cancer (NSCLC). In primary NSCLC cells and established cell lines, Lnc-THOR shRNA or CRISPR/Cas9-mediated knockout (KO) downregulated IGF2BP1 target mRNAs (IGF2, Gli1, Myc and SOX9), inhibiting cell viability, growth, proliferation, migration and invasion. Significant apoptosis activation was detected in Lnc-THOR-silenced/-KO NSCLC cells. Conversely, ectopic overexpression of Lnc-THOR upregulated IGF2BP1 mRNA targets and enhanced NSCLC cell proliferation, migration and invasion. RNA-immunoprecipitation and RNA pull-down assay results confirmed the direct binding between Lnc-THOR and IGF2BP1 protein in NSCLC cells. Lnc-THOR silencing and overexpression were ineffective in IGF2BP1-KO NSCLC cells. Forced IGF2BP1 overexpression failed to rescue Lnc-THOR-KO NSCLC cells. In vivo, intratumoral injection of Lnc-THOR shRNA adeno-associated virus potently inhibited A549 xenograft tumor growth in nude mice. At last we show that Lnc-THOR is overexpressed in multiple NSCLC tissues and established/primary NSCLC cells. Collectively, these results highlighted the ability of Lnc-THOR in promoting NSCLC cell growth by associating with IGF2BP1, suggesting that Lnc-THOR represents a promising therapeutic target of NSCLC.
format	article
author	Peng-Fei Jiao Pei-jun Tang Dan Chu Ya-meng Li Wei-hua Xu Gao-Fei Ren
author_facet	Peng-Fei Jiao Pei-jun Tang Dan Chu Ya-meng Li Wei-hua Xu Gao-Fei Ren
author_sort	Peng-Fei Jiao
title	Long Non-Coding RNA THOR Depletion Inhibits Human Non-Small Cell Lung Cancer Cell Growth
title_short	Long Non-Coding RNA THOR Depletion Inhibits Human Non-Small Cell Lung Cancer Cell Growth
title_full	Long Non-Coding RNA THOR Depletion Inhibits Human Non-Small Cell Lung Cancer Cell Growth
title_fullStr	Long Non-Coding RNA THOR Depletion Inhibits Human Non-Small Cell Lung Cancer Cell Growth
title_full_unstemmed	Long Non-Coding RNA THOR Depletion Inhibits Human Non-Small Cell Lung Cancer Cell Growth
title_sort	long non-coding rna thor depletion inhibits human non-small cell lung cancer cell growth
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/5e82f97a570f4966933e7f7adbcf7bee
work_keys_str_mv	AT pengfeijiao longnoncodingrnathordepletioninhibitshumannonsmallcelllungcancercellgrowth AT peijuntang longnoncodingrnathordepletioninhibitshumannonsmallcelllungcancercellgrowth AT danchu longnoncodingrnathordepletioninhibitshumannonsmallcelllungcancercellgrowth AT yamengli longnoncodingrnathordepletioninhibitshumannonsmallcelllungcancercellgrowth AT weihuaxu longnoncodingrnathordepletioninhibitshumannonsmallcelllungcancercellgrowth AT gaofeiren longnoncodingrnathordepletioninhibitshumannonsmallcelllungcancercellgrowth
_version_	1718425927350747136

Long Non-Coding RNA THOR Depletion Inhibits Human Non-Small Cell Lung Cancer Cell Growth

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