KLF5 activates lncRNA DANCR and inhibits cancer cell autophagy accelerating gastric cancer progression

Abstract Cancer cell autophagy has been associated with the progression of gastric cancer (GC), but involvement of long noncoding RNAs (lncRNAs) remains unclear. Initial bioinformatics analysis has identified abnormally highly expressed KLF5 in GC, as well as the predicted regulatory mechanism assoc...

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Autores principales:	Zhiyi Cheng, Guiyuan Liu, Chuanjiang Huang, Xiaojun Zhao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Genetics QH426-470
Acceso en línea:	https://doaj.org/article/d11987d50efb40a6be90afebc5c03e45
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spelling	oai:doaj.org-article:d11987d50efb40a6be90afebc5c03e452021-12-02T15:13:48ZKLF5 activates lncRNA DANCR and inhibits cancer cell autophagy accelerating gastric cancer progression10.1038/s41525-021-00207-72056-7944https://doaj.org/article/d11987d50efb40a6be90afebc5c03e452021-09-01T00:00:00Zhttps://doi.org/10.1038/s41525-021-00207-7https://doaj.org/toc/2056-7944Abstract Cancer cell autophagy has been associated with the progression of gastric cancer (GC), but involvement of long noncoding RNAs (lncRNAs) remains unclear. Initial bioinformatics analysis has identified abnormally highly expressed KLF5 in GC, as well as the predicted regulatory mechanism associating with lncRNA DANCR, miR-194, and AKT2. The expression of KLF5, DANCR, and AKT2 in GC tissue was upregulated, and the expression of miR-194 was downregulated. We knocked KLF5 down and manipulated the expression of DANCR, miR-194, and AKT2 to characterize their roles in GC cell viability, autophagy, and apoptosis. The mechanistic investigations revealed that KLF5 activated the transcription of DANCR in the promoter region and elevated its expression. DANCR acted as a miR-194 sponge to repress its expression in GC. MiR-194 targeted and inhibited AKT2 expression. Silencing KLF5 augmented GC cell autophagy, apoptosis and impeded its viability through the DANCR/miR-194/AKT2 axis. The tumor-inhibiting properties of KLF5 knockdown were substantiated in vivo. Together, our study uncovered the oncogenic role of KLF5-dependent lncRNA DANCR transcription in GC in vivo and in vitro, which implicates the miR-194/AKT2 axis in tumor growth regulation, and it may be a potential therapeutic target for human GC.Zhiyi ChengGuiyuan LiuChuanjiang HuangXiaojun ZhaoNature PortfolioarticleMedicineRGeneticsQH426-470ENnpj Genomic Medicine, Vol 6, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Genetics QH426-470
spellingShingle	Medicine R Genetics QH426-470 Zhiyi Cheng Guiyuan Liu Chuanjiang Huang Xiaojun Zhao KLF5 activates lncRNA DANCR and inhibits cancer cell autophagy accelerating gastric cancer progression
description	Abstract Cancer cell autophagy has been associated with the progression of gastric cancer (GC), but involvement of long noncoding RNAs (lncRNAs) remains unclear. Initial bioinformatics analysis has identified abnormally highly expressed KLF5 in GC, as well as the predicted regulatory mechanism associating with lncRNA DANCR, miR-194, and AKT2. The expression of KLF5, DANCR, and AKT2 in GC tissue was upregulated, and the expression of miR-194 was downregulated. We knocked KLF5 down and manipulated the expression of DANCR, miR-194, and AKT2 to characterize their roles in GC cell viability, autophagy, and apoptosis. The mechanistic investigations revealed that KLF5 activated the transcription of DANCR in the promoter region and elevated its expression. DANCR acted as a miR-194 sponge to repress its expression in GC. MiR-194 targeted and inhibited AKT2 expression. Silencing KLF5 augmented GC cell autophagy, apoptosis and impeded its viability through the DANCR/miR-194/AKT2 axis. The tumor-inhibiting properties of KLF5 knockdown were substantiated in vivo. Together, our study uncovered the oncogenic role of KLF5-dependent lncRNA DANCR transcription in GC in vivo and in vitro, which implicates the miR-194/AKT2 axis in tumor growth regulation, and it may be a potential therapeutic target for human GC.
format	article
author	Zhiyi Cheng Guiyuan Liu Chuanjiang Huang Xiaojun Zhao
author_facet	Zhiyi Cheng Guiyuan Liu Chuanjiang Huang Xiaojun Zhao
author_sort	Zhiyi Cheng
title	KLF5 activates lncRNA DANCR and inhibits cancer cell autophagy accelerating gastric cancer progression
title_short	KLF5 activates lncRNA DANCR and inhibits cancer cell autophagy accelerating gastric cancer progression
title_full	KLF5 activates lncRNA DANCR and inhibits cancer cell autophagy accelerating gastric cancer progression
title_fullStr	KLF5 activates lncRNA DANCR and inhibits cancer cell autophagy accelerating gastric cancer progression
title_full_unstemmed	KLF5 activates lncRNA DANCR and inhibits cancer cell autophagy accelerating gastric cancer progression
title_sort	klf5 activates lncrna dancr and inhibits cancer cell autophagy accelerating gastric cancer progression
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d11987d50efb40a6be90afebc5c03e45
work_keys_str_mv	AT zhiyicheng klf5activateslncrnadancrandinhibitscancercellautophagyacceleratinggastriccancerprogression AT guiyuanliu klf5activateslncrnadancrandinhibitscancercellautophagyacceleratinggastriccancerprogression AT chuanjianghuang klf5activateslncrnadancrandinhibitscancercellautophagyacceleratinggastriccancerprogression AT xiaojunzhao klf5activateslncrnadancrandinhibitscancercellautophagyacceleratinggastriccancerprogression
_version_	1718387600203448320

KLF5 activates lncRNA DANCR and inhibits cancer cell autophagy accelerating gastric cancer progression

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