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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MDPI AG
2023-02-01
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| Series: | Toxics |
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| author | Xinglei Huang Zhaohui Su Jiangheng Li Junquan He Na Zhao Liyun Nie Bin Guan Qiuyue Huang Huiliu Zhao Guo-Dong Lu Qingqing Nong |
| author_facet | Xinglei Huang Zhaohui Su Jiangheng Li Junquan He Na Zhao Liyun Nie Bin Guan Qiuyue Huang Huiliu Zhao Guo-Dong Lu Qingqing Nong |
| author_sort | Xinglei Huang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T08:03:44Z |
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| id | doaj.art-579ba4017fe642ed993c2d6600eb8a72 |
| institution | Directory Open Access Journal |
| issn | 2305-6304 |
| language | English |
| last_indexed | 2024-03-11T08:03:44Z |
| publishDate | 2023-02-01 |
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| series | Toxics |
| spelling | doaj.art-579ba4017fe642ed993c2d6600eb8a722023-11-16T23:37:48ZengMDPI AGToxics2305-63042023-02-0111216210.3390/toxics11020162Downregulation of LncRNA GCLC-1 Promotes Microcystin-LR-Induced Malignant Transformation of Human Liver Cells by Regulating GCLC ExpressionXinglei Huang0Zhaohui Su1Jiangheng Li2Junquan He3Na Zhao4Liyun Nie5Bin Guan6Qiuyue Huang7Huiliu Zhao8Guo-Dong Lu9Qingqing Nong10Department of Environmental Health, School of Public Health, Guangxi Medical University, Nanning 530021, ChinaDepartment of Environmental Health, School of Public Health, Guangxi Medical University, Nanning 530021, ChinaDepartment of Environmental Health, School of Public Health, Guangxi Medical University, Nanning 530021, ChinaDepartment of Environmental Health, School of Public Health, Guangxi Medical University, Nanning 530021, ChinaDepartment of Environmental Health, School of Public Health, Guangxi Medical University, Nanning 530021, ChinaDepartment of Environmental Health, School of Public Health, Guangxi Medical University, Nanning 530021, ChinaDepartment of Environmental Health, School of Public Health, Guangxi Medical University, Nanning 530021, ChinaDepartment of Environmental Health, School of Public Health, Guangxi Medical University, Nanning 530021, ChinaDepartment of Clinical Laboratory, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, ChinaDepartment of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, ChinaDepartment of Environmental Health, School of Public Health, Guangxi Medical University, Nanning 530021, ChinaMicrocystin-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.https://www.mdpi.com/2305-6304/11/2/162microcystin-LRlncRNA GCLC-1GCLCcarcinogenesis |
| spellingShingle | Xinglei Huang Zhaohui Su Jiangheng Li Junquan He Na Zhao Liyun Nie Bin Guan Qiuyue Huang Huiliu Zhao Guo-Dong Lu Qingqing Nong Downregulation of LncRNA GCLC-1 Promotes Microcystin-LR-Induced Malignant Transformation of Human Liver Cells by Regulating GCLC Expression Toxics microcystin-LR lncRNA GCLC-1 GCLC carcinogenesis |
| 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 | microcystin-LR lncRNA GCLC-1 GCLC carcinogenesis |
| url | https://www.mdpi.com/2305-6304/11/2/162 |
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