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Up-Regulated Expression of Pro-Apoptotic Long Noncoding RNA lincRNA-p21 with Enhanced Cell Apoptosis in Lupus Nephritis
Accelerated cell apoptosis with dysregulated long noncoding RNAs is the crucial pathogenesis in lupus nephritis (LN). Pro-apoptotic lincRNA-p21 was studied in LN patients, cell lines with lentivirus-mediated overexpression and CRISPR interference (CRISPRi)-conducted repression, and a mouse model. Cl...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795010/ https://www.ncbi.nlm.nih.gov/pubmed/33396699 http://dx.doi.org/10.3390/ijms22010301 |
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author | Chen, Yi-Cheng Kuo, Pin-Yu Chou, Yu-Chi Chong, Hao-Earn Hsieh, Yu-Tung Yang, Mei-Lin Wu, Chao-Liang Shiau, Ai-Li Wang, Chrong-Reen |
author_facet | Chen, Yi-Cheng Kuo, Pin-Yu Chou, Yu-Chi Chong, Hao-Earn Hsieh, Yu-Tung Yang, Mei-Lin Wu, Chao-Liang Shiau, Ai-Li Wang, Chrong-Reen |
author_sort | Chen, Yi-Cheng |
collection | PubMed |
description | Accelerated cell apoptosis with dysregulated long noncoding RNAs is the crucial pathogenesis in lupus nephritis (LN). Pro-apoptotic lincRNA-p21 was studied in LN patients, cell lines with lentivirus-mediated overexpression and CRISPR interference (CRISPRi)-conducted repression, and a mouse model. Clinical samples were from patients and age/sex-matched controls. Expression of lincRNA-p21 and endogenous RNA target miR-181a, were examined in mononuclear and urine cells. Guide RNA sequences targeting lincRNA-p21 were cloned into CRISPRi with dCas9/ Krüppel-associated box (KRAB) domain. LincRNA-p21-silened transfectants were investigated for apoptosis and miR-181a expression. LincRNA-p21-overexpressed cells were evaluated for apoptosis and p53-related down-stream molecules. Balb/C mice were injected with pristane to induce LN and examined for apoptosis and lincRNA-p21. Higher lincRNA-p21 levels were found in LN mononuclear and urine cells, positively correlated with activity. There were lower miR-181a levels in LN mononuclear cells, negatively correlated with activity. Doxorubicin-induced apoptotic cells had up-regulated lincRNA-p21 levels. CRISPRi with dCas9/KARA domain showed efficient repression ability on transcription initiation/elongation. CRISPRi-conducted lincRNA-p21-silenced transfectants displayed reduced apoptosis with up-regulated miR-181a levels, whereas lentivirus-mediated lincRNA-p21-overexpressed cells revealed enhanced apoptosis with up-regulated downstream PUMA/Bax expression. LN mice had glomerular apoptosis with progressive increased lincRNA-p21 levels. Our results demonstrate up-regulated lincRNA-p21 expression in LN, implicating a potential diagnostic marker and therapeutic target. |
format | Online Article Text |
id | pubmed-7795010 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77950102021-01-10 Up-Regulated Expression of Pro-Apoptotic Long Noncoding RNA lincRNA-p21 with Enhanced Cell Apoptosis in Lupus Nephritis Chen, Yi-Cheng Kuo, Pin-Yu Chou, Yu-Chi Chong, Hao-Earn Hsieh, Yu-Tung Yang, Mei-Lin Wu, Chao-Liang Shiau, Ai-Li Wang, Chrong-Reen Int J Mol Sci Article Accelerated cell apoptosis with dysregulated long noncoding RNAs is the crucial pathogenesis in lupus nephritis (LN). Pro-apoptotic lincRNA-p21 was studied in LN patients, cell lines with lentivirus-mediated overexpression and CRISPR interference (CRISPRi)-conducted repression, and a mouse model. Clinical samples were from patients and age/sex-matched controls. Expression of lincRNA-p21 and endogenous RNA target miR-181a, were examined in mononuclear and urine cells. Guide RNA sequences targeting lincRNA-p21 were cloned into CRISPRi with dCas9/ Krüppel-associated box (KRAB) domain. LincRNA-p21-silened transfectants were investigated for apoptosis and miR-181a expression. LincRNA-p21-overexpressed cells were evaluated for apoptosis and p53-related down-stream molecules. Balb/C mice were injected with pristane to induce LN and examined for apoptosis and lincRNA-p21. Higher lincRNA-p21 levels were found in LN mononuclear and urine cells, positively correlated with activity. There were lower miR-181a levels in LN mononuclear cells, negatively correlated with activity. Doxorubicin-induced apoptotic cells had up-regulated lincRNA-p21 levels. CRISPRi with dCas9/KARA domain showed efficient repression ability on transcription initiation/elongation. CRISPRi-conducted lincRNA-p21-silenced transfectants displayed reduced apoptosis with up-regulated miR-181a levels, whereas lentivirus-mediated lincRNA-p21-overexpressed cells revealed enhanced apoptosis with up-regulated downstream PUMA/Bax expression. LN mice had glomerular apoptosis with progressive increased lincRNA-p21 levels. Our results demonstrate up-regulated lincRNA-p21 expression in LN, implicating a potential diagnostic marker and therapeutic target. MDPI 2020-12-30 /pmc/articles/PMC7795010/ /pubmed/33396699 http://dx.doi.org/10.3390/ijms22010301 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chen, Yi-Cheng Kuo, Pin-Yu Chou, Yu-Chi Chong, Hao-Earn Hsieh, Yu-Tung Yang, Mei-Lin Wu, Chao-Liang Shiau, Ai-Li Wang, Chrong-Reen Up-Regulated Expression of Pro-Apoptotic Long Noncoding RNA lincRNA-p21 with Enhanced Cell Apoptosis in Lupus Nephritis |
title | Up-Regulated Expression of Pro-Apoptotic Long Noncoding RNA lincRNA-p21 with Enhanced Cell Apoptosis in Lupus Nephritis |
title_full | Up-Regulated Expression of Pro-Apoptotic Long Noncoding RNA lincRNA-p21 with Enhanced Cell Apoptosis in Lupus Nephritis |
title_fullStr | Up-Regulated Expression of Pro-Apoptotic Long Noncoding RNA lincRNA-p21 with Enhanced Cell Apoptosis in Lupus Nephritis |
title_full_unstemmed | Up-Regulated Expression of Pro-Apoptotic Long Noncoding RNA lincRNA-p21 with Enhanced Cell Apoptosis in Lupus Nephritis |
title_short | Up-Regulated Expression of Pro-Apoptotic Long Noncoding RNA lincRNA-p21 with Enhanced Cell Apoptosis in Lupus Nephritis |
title_sort | up-regulated expression of pro-apoptotic long noncoding rna lincrna-p21 with enhanced cell apoptosis in lupus nephritis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795010/ https://www.ncbi.nlm.nih.gov/pubmed/33396699 http://dx.doi.org/10.3390/ijms22010301 |
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