LncRNA MIR503HG Promotes High-Glucose-Induced Proximal Tubular Cell Apoptosis by Targeting miR-503-5p/Bcl-2 Pathway

Xu Cao, Qiu-Ling Fan Department of Nephrology, The First Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Qiu-Ling FanDepartment of Nephrology, The First Hospital of China Medical University, No. 155 Nanjing Bei Street, Heping District, Shenyang 110...

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Autores principales:	Cao X, Fan QL
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	diabetic nephropathy lncrna mir503hg mir-503 host gene apoptosis Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/0ebb9fb87cd541f1b709407e8dc600d4
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spelling	oai:doaj.org-article:0ebb9fb87cd541f1b709407e8dc600d42021-12-02T16:05:13ZLncRNA MIR503HG Promotes High-Glucose-Induced Proximal Tubular Cell Apoptosis by Targeting miR-503-5p/Bcl-2 Pathway1178-7007https://doaj.org/article/0ebb9fb87cd541f1b709407e8dc600d42020-11-01T00:00:00Zhttps://www.dovepress.com/lncrna-mir503hg-promotes-high-glucose-induced-proximal-tubular-cell-ap-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Xu Cao, Qiu-Ling Fan Department of Nephrology, The First Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Qiu-Ling FanDepartment of Nephrology, The First Hospital of China Medical University, No. 155 Nanjing Bei Street, Heping District, Shenyang 110001, People’s Republic of ChinaTel +86 13904012680Email cmufql@163.comAim: More than half of microRNAs are located in genes. LncRNAs are host genes of intronic microRNAs that regulate intracellular splicing to form pre-miRNAs that are processed to mature miRNAs. MicroRNAs work as partners or antagonists of their host lncRNAs by fine-tuning their target genes. However, whether lncRNA-MIR503HG (miR-503 host gene) is co-transcribed with miR-503 and affects miR-503 splicing, thereby affecting its target gene Bcl-2 expression and cell mitochondrial apoptotic pathway in diabetic nephropathy (DN) is currently unknown.Methods: Human proximal tubular (HK-2) cells cultured in high glucose were transfected with lncRNA MIR503HG overexpression/inhibition plasmid and miR-503 mimics/inhibitor. Real-time quantitative PCR was used to measure the expression levels of lncRNA MIR503HG, pre-miR-503, miR-503 and Bcl-2. Western blot was used to measure the protein expressions of Bcl-2, Bax, Cytc and cleaved-caspase 9/3. Annexin V/PI flow cytometry was used to measure apoptosis.Results: Host lncRNA MIR503HG was co-transcribed with miR-503. MIR503HG regulated the expression of miR-503 by affecting miR-503 splicing synthesis. In the presence of high glucose, the expression levels of lncRNA MIR503HG and miR-503 were up-regulated in HK-2 cells cultured in high glucose. Bcl-2 expression was inhibited and levels of apoptosis-related proteins Cytc and Bax were increased in HK-2 cells cultured in high glucose, all of which promoted the caspase cascade reaction, leading to increased caspase-9 and caspase-3 shear fragments inducing apoptosis of the mitochondrial pathway. Inhibition of MIR503HG led to a reduction in miR-503 expression, up-regulated its target gene Bcl-2, inhibited the expression levels of Bax and other apoptosis-related proteins and attenuated HK-2 cell apoptosis induced by high glucose. Co-transfection of miRNA-503 partially offset the effect of MIR503HG-siRNA.Conclusion: MIR503HG indirectly regulates Bcl-2 by promoting the co-transcription of miRNA-503 to participate high-glucose-induced proximal tubular cell apoptosis, providing a new target for diabetic nephropathy treatment.Keywords: diabetic nephropathy, lncRNA MIR503HG, miR-503, host gene, apoptosisCao XFan QLDove Medical Pressarticlediabetic nephropathylncrna mir503hgmir-503host geneapoptosisSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 13, Pp 4507-4517 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	diabetic nephropathy lncrna mir503hg mir-503 host gene apoptosis Specialties of internal medicine RC581-951
spellingShingle	diabetic nephropathy lncrna mir503hg mir-503 host gene apoptosis Specialties of internal medicine RC581-951 Cao X Fan QL LncRNA MIR503HG Promotes High-Glucose-Induced Proximal Tubular Cell Apoptosis by Targeting miR-503-5p/Bcl-2 Pathway
description	Xu Cao, Qiu-Ling Fan Department of Nephrology, The First Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Qiu-Ling FanDepartment of Nephrology, The First Hospital of China Medical University, No. 155 Nanjing Bei Street, Heping District, Shenyang 110001, People’s Republic of ChinaTel +86 13904012680Email cmufql@163.comAim: More than half of microRNAs are located in genes. LncRNAs are host genes of intronic microRNAs that regulate intracellular splicing to form pre-miRNAs that are processed to mature miRNAs. MicroRNAs work as partners or antagonists of their host lncRNAs by fine-tuning their target genes. However, whether lncRNA-MIR503HG (miR-503 host gene) is co-transcribed with miR-503 and affects miR-503 splicing, thereby affecting its target gene Bcl-2 expression and cell mitochondrial apoptotic pathway in diabetic nephropathy (DN) is currently unknown.Methods: Human proximal tubular (HK-2) cells cultured in high glucose were transfected with lncRNA MIR503HG overexpression/inhibition plasmid and miR-503 mimics/inhibitor. Real-time quantitative PCR was used to measure the expression levels of lncRNA MIR503HG, pre-miR-503, miR-503 and Bcl-2. Western blot was used to measure the protein expressions of Bcl-2, Bax, Cytc and cleaved-caspase 9/3. Annexin V/PI flow cytometry was used to measure apoptosis.Results: Host lncRNA MIR503HG was co-transcribed with miR-503. MIR503HG regulated the expression of miR-503 by affecting miR-503 splicing synthesis. In the presence of high glucose, the expression levels of lncRNA MIR503HG and miR-503 were up-regulated in HK-2 cells cultured in high glucose. Bcl-2 expression was inhibited and levels of apoptosis-related proteins Cytc and Bax were increased in HK-2 cells cultured in high glucose, all of which promoted the caspase cascade reaction, leading to increased caspase-9 and caspase-3 shear fragments inducing apoptosis of the mitochondrial pathway. Inhibition of MIR503HG led to a reduction in miR-503 expression, up-regulated its target gene Bcl-2, inhibited the expression levels of Bax and other apoptosis-related proteins and attenuated HK-2 cell apoptosis induced by high glucose. Co-transfection of miRNA-503 partially offset the effect of MIR503HG-siRNA.Conclusion: MIR503HG indirectly regulates Bcl-2 by promoting the co-transcription of miRNA-503 to participate high-glucose-induced proximal tubular cell apoptosis, providing a new target for diabetic nephropathy treatment.Keywords: diabetic nephropathy, lncRNA MIR503HG, miR-503, host gene, apoptosis
format	article
author	Cao X Fan QL
author_facet	Cao X Fan QL
author_sort	Cao X
title	LncRNA MIR503HG Promotes High-Glucose-Induced Proximal Tubular Cell Apoptosis by Targeting miR-503-5p/Bcl-2 Pathway
title_short	LncRNA MIR503HG Promotes High-Glucose-Induced Proximal Tubular Cell Apoptosis by Targeting miR-503-5p/Bcl-2 Pathway
title_full	LncRNA MIR503HG Promotes High-Glucose-Induced Proximal Tubular Cell Apoptosis by Targeting miR-503-5p/Bcl-2 Pathway
title_fullStr	LncRNA MIR503HG Promotes High-Glucose-Induced Proximal Tubular Cell Apoptosis by Targeting miR-503-5p/Bcl-2 Pathway
title_full_unstemmed	LncRNA MIR503HG Promotes High-Glucose-Induced Proximal Tubular Cell Apoptosis by Targeting miR-503-5p/Bcl-2 Pathway
title_sort	lncrna mir503hg promotes high-glucose-induced proximal tubular cell apoptosis by targeting mir-503-5p/bcl-2 pathway
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/0ebb9fb87cd541f1b709407e8dc600d4
work_keys_str_mv	AT caox lncrnamir503hgpromoteshighglucoseinducedproximaltubularcellapoptosisbytargetingmir5035pbcl2pathway AT fanql lncrnamir503hgpromoteshighglucoseinducedproximaltubularcellapoptosisbytargetingmir5035pbcl2pathway
_version_	1718385190846332928

LncRNA MIR503HG Promotes High-Glucose-Induced Proximal Tubular Cell Apoptosis by Targeting miR-503-5p/Bcl-2 Pathway

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