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Downregulation of LncRNA GCLC-1 Promotes Microcystin-LR-Induced Malignant Transformation of Human Liver Cells by Regulating GCLC Expression

Microcystin-LR (MCLR) is an aquatic toxin, which could lead to the development of hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) are considered important regulatory elements in the occurrence and development of cancer. However, the roles and mechanisms of lncRNAs during the process o...

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Autores principales: Huang, Xinglei, Su, Zhaohui, Li, Jiangheng, He, Junquan, Zhao, Na, Nie, Liyun, Guan, Bin, Huang, Qiuyue, Zhao, Huiliu, Lu, Guo-Dong, Nong, Qingqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9960881/
https://www.ncbi.nlm.nih.gov/pubmed/36851037
http://dx.doi.org/10.3390/toxics11020162
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author Huang, Xinglei
Su, Zhaohui
Li, Jiangheng
He, Junquan
Zhao, Na
Nie, Liyun
Guan, Bin
Huang, Qiuyue
Zhao, Huiliu
Lu, Guo-Dong
Nong, Qingqing
author_facet Huang, Xinglei
Su, Zhaohui
Li, Jiangheng
He, Junquan
Zhao, Na
Nie, Liyun
Guan, Bin
Huang, Qiuyue
Zhao, Huiliu
Lu, Guo-Dong
Nong, Qingqing
author_sort Huang, Xinglei
collection PubMed
description Microcystin-LR (MCLR) is an aquatic toxin, which could lead to the development of hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) are considered important regulatory elements in the occurrence and development of cancer. However, the roles and mechanisms of lncRNAs during the process of HCC, induced by MCLR, remain elusive. Here, we identified a novel lncRNA, namely lnc-GCLC-1 (lncGCLC), which is in close proximity to the chromosome location of glutamate–cysteine ligase catalytic subunit (GCLC). We then investigated the role of lncGCLC in MCLR-induced malignant transformation of WRL68, a human hepatic cell line. During MCLR-induced cell transformation, the expression of lncGCLC and GCLC decreased continuously, accompanied with a consistently high expression of miR-122-5p. Knockdown of lncGCLC promoted cell proliferation, migration and invasion, but reduced cell apoptosis. A xenograft nude mouse model demonstrated that knockdown of lncGCLC promoted tumor growth. Furthermore, knockdown of lncGCLC significantly upregulated miR-122-5p expression, suppressed GCLC expression and GSH levels, and enhanced oxidative DNA damages. More importantly, the expression of lncGCLC in human HCC tissues was significantly downregulated in the high-microcystin exposure group, and positively associated with GCLC level in HCC tissues. Together, these findings suggest that lncGCLC plays an anti-oncogenic role in MCLR-induced malignant transformation by regulating GCLC expression.
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spelling pubmed-99608812023-02-26 Downregulation of LncRNA GCLC-1 Promotes Microcystin-LR-Induced Malignant Transformation of Human Liver Cells by Regulating GCLC Expression Huang, Xinglei Su, Zhaohui Li, Jiangheng He, Junquan Zhao, Na Nie, Liyun Guan, Bin Huang, Qiuyue Zhao, Huiliu Lu, Guo-Dong Nong, Qingqing Toxics Article Microcystin-LR (MCLR) is an aquatic toxin, which could lead to the development of hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) are considered important regulatory elements in the occurrence and development of cancer. However, the roles and mechanisms of lncRNAs during the process of HCC, induced by MCLR, remain elusive. Here, we identified a novel lncRNA, namely lnc-GCLC-1 (lncGCLC), which is in close proximity to the chromosome location of glutamate–cysteine ligase catalytic subunit (GCLC). We then investigated the role of lncGCLC in MCLR-induced malignant transformation of WRL68, a human hepatic cell line. During MCLR-induced cell transformation, the expression of lncGCLC and GCLC decreased continuously, accompanied with a consistently high expression of miR-122-5p. Knockdown of lncGCLC promoted cell proliferation, migration and invasion, but reduced cell apoptosis. A xenograft nude mouse model demonstrated that knockdown of lncGCLC promoted tumor growth. Furthermore, knockdown of lncGCLC significantly upregulated miR-122-5p expression, suppressed GCLC expression and GSH levels, and enhanced oxidative DNA damages. More importantly, the expression of lncGCLC in human HCC tissues was significantly downregulated in the high-microcystin exposure group, and positively associated with GCLC level in HCC tissues. Together, these findings suggest that lncGCLC plays an anti-oncogenic role in MCLR-induced malignant transformation by regulating GCLC expression. MDPI 2023-02-09 /pmc/articles/PMC9960881/ /pubmed/36851037 http://dx.doi.org/10.3390/toxics11020162 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Huang, Xinglei
Su, Zhaohui
Li, Jiangheng
He, Junquan
Zhao, Na
Nie, Liyun
Guan, Bin
Huang, Qiuyue
Zhao, Huiliu
Lu, Guo-Dong
Nong, Qingqing
Downregulation of LncRNA GCLC-1 Promotes Microcystin-LR-Induced Malignant Transformation of Human Liver Cells by Regulating GCLC Expression
title Downregulation of LncRNA GCLC-1 Promotes Microcystin-LR-Induced Malignant Transformation of Human Liver Cells by Regulating GCLC Expression
title_full Downregulation of LncRNA GCLC-1 Promotes Microcystin-LR-Induced Malignant Transformation of Human Liver Cells by Regulating GCLC Expression
title_fullStr Downregulation of LncRNA GCLC-1 Promotes Microcystin-LR-Induced Malignant Transformation of Human Liver Cells by Regulating GCLC Expression
title_full_unstemmed Downregulation of LncRNA GCLC-1 Promotes Microcystin-LR-Induced Malignant Transformation of Human Liver Cells by Regulating GCLC Expression
title_short Downregulation of LncRNA GCLC-1 Promotes Microcystin-LR-Induced Malignant Transformation of Human Liver Cells by Regulating GCLC Expression
title_sort downregulation of lncrna gclc-1 promotes microcystin-lr-induced malignant transformation of human liver cells by regulating gclc expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9960881/
https://www.ncbi.nlm.nih.gov/pubmed/36851037
http://dx.doi.org/10.3390/toxics11020162
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