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Volume 11
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10.3390/toxics11020162
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Article

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

by
Xinglei Huang
1,†,
Zhaohui Su
1,†,
Jiangheng Li
1,
Junquan He
1,
Na Zhao
1,
Liyun Nie
1,
Bin Guan
1,
Qiuyue Huang
1,
Huiliu Zhao
2,
Guo-Dong Lu
3 and
Qingqing Nong
1,4,5,*
1
Department of Environmental Health, School of Public Health, Guangxi Medical University, Nanning 530021, China
2
Department of Clinical Laboratory, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China
3
Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China
4
Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning 530021, China
5
Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning 530021, China
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Toxics 2023, 11(2), 162; https://doi.org/10.3390/toxics11020162
Submission received: 21 December 2022 / Revised: 3 February 2023 / Accepted: 5 February 2023 / Published: 9 February 2023
(This article belongs to the Topic Environmental Toxicology and Human Health)
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Abstract

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.
Keywords: microcystin-LR; lncRNA GCLC-1; GCLC; carcinogenesis microcystin-LR; lncRNA GCLC-1; GCLC; carcinogenesis

Share and Cite

MDPI and ACS Style

Huang, X.; Su, Z.; Li, J.; He, J.; Zhao, N.; Nie, L.; Guan, B.; Huang, Q.; Zhao, H.; Lu, G.-D.; et al. Downregulation of LncRNA GCLC-1 Promotes Microcystin-LR-Induced Malignant Transformation of Human Liver Cells by Regulating GCLC Expression. Toxics 2023, 11, 162. https://doi.org/10.3390/toxics11020162

AMA Style

Huang X, Su Z, Li J, He J, Zhao N, Nie L, Guan B, Huang Q, Zhao H, Lu G-D, et al. Downregulation of LncRNA GCLC-1 Promotes Microcystin-LR-Induced Malignant Transformation of Human Liver Cells by Regulating GCLC Expression. Toxics. 2023; 11(2):162. https://doi.org/10.3390/toxics11020162

Chicago/Turabian Style

Huang, Xinglei, Zhaohui Su, Jiangheng Li, Junquan He, Na Zhao, Liyun Nie, Bin Guan, Qiuyue Huang, Huiliu Zhao, Guo-Dong Lu, and et al. 2023. "Downregulation of LncRNA GCLC-1 Promotes Microcystin-LR-Induced Malignant Transformation of Human Liver Cells by Regulating GCLC Expression" Toxics 11, no. 2: 162. https://doi.org/10.3390/toxics11020162

APA Style

Huang, X., Su, Z., Li, J., He, J., Zhao, N., Nie, L., Guan, B., Huang, Q., Zhao, H., Lu, G.-D., & Nong, Q. (2023). Downregulation of LncRNA GCLC-1 Promotes Microcystin-LR-Induced Malignant Transformation of Human Liver Cells by Regulating GCLC Expression. Toxics, 11(2), 162. https://doi.org/10.3390/toxics11020162

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