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...

Full description

Saved in:
Bibliographic Details
Published in:Toxics (Basel) 2023-02, Vol.11 (2), p.162
Main Authors: Huang, Xinglei, Su, Zhaohui, Li, Jiangheng, He, Junquan, Zhao, Na, Nie, Liyun, Guan, Bin, Huang, Qiuyue, Zhao, Huiliu, Lu, Guo-Dong, Nong, Qingqing
Format: Article
Language:English
Subjects:
Anti-oncogenes
Apoptosis
Cancer
carcinogenesis
Cell cycle
Cell growth
Cell migration
Cell proliferation
Chromosomes
Development and progression
Environmental aspects
Enzymes
Flow cytometry
GCLC
Gene expression
Genetic transformation
Health aspects
Hepatocellular carcinoma
Hepatocytes
Hepatoma
Liver cancer
lncRNA GCLC-1
Microcystin-LR
Microcystins
Microcystis
Mitochondrial DNA
Non-coding RNA
Oxidative stress
Reagents
Regulatory sequences
Risk factors
Toxins
Transformations
Tumors
Xenografts
Xenotransplantation
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2305-6304
2305-6304
DOI:10.3390/toxics11020162