Regulation of Microcystin-LR-Induced DNA Damage by miR-451a in HL7702 Cells

Lv Chen; Shu Yang; Cong Wen; Shuilin Zheng; Yue Yang; Xiangling Feng; Jihua Chen; Dan Luo; Ran Liu; Fei Yang

doi:10.3390/toxins11030164

Regulation of Microcystin-LR-Induced DNA Damage by miR-451a in HL7702 Cells

Toxins (Basel). 2019 Mar 15;11(3):164. doi: 10.3390/toxins11030164.

Authors

Lv Chen¹, Shu Yang², Cong Wen³, Shuilin Zheng⁴, Yue Yang⁵, Xiangling Feng⁶, Jihua Chen⁷, Dan Luo⁸, Ran Liu⁹, Fei Yang^{10

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Affiliations

¹ Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha 410078, China. chenlv@csu.edu.cn.
² Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha 410078, China. 18773152460@163.com.
³ Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha 410078, China. wencong941017@csu.edu.cn.
⁴ Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha 410078, China. zhengshl@csu.edu.cn.
⁵ Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha 410078, China. yangy930806@gmail.com.
⁶ Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha 410078, China. fengxl2011@csu.edu.cn.
⁷ Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha 410078, China. chenjh@csu.edu.cn.
⁸ Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha 410078, China. luodan_csu_2011@126.com.
⁹ Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health Southeast University, Nanjing 210007, China. ranliu@seu.edu.cn.
¹⁰ Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha 410078, China. phfyang@csu.edu.cn.
¹¹ Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health Southeast University, Nanjing 210007, China. phfyang@csu.edu.cn.
¹² Key laboratory of Hunan Province for Water Environment and Agriculture Product Safety, Central South University, Changsha 410083, China. phfyang@csu.edu.cn.

Abstract

Microcystin-LR is a cyclic heptapeptide hepatotoxin produced by harmful cyanobacteria. A panel of microRNAs containing miR-451a were found to be significantly changed in normal human liver cells HL7702 after exposure to microcystin-LR (MC-LR) in our previous study. However, the functions of miR-451a in hepatotoxicity induced by MC-LR remained unclear. The study aimed to investigate the impacts of miR-451a in HL7702 cells following treatment with 5 or 10 μM MC-LR. The comet assay indicated that MC-LR can influence Olive tail moment (OTM) in HL7702 cells. Furthermore, increase of miR-451a significantly repressed DNA damage and the protein expression level of γ-H2AX induced by MC-LR. Moreover, over-expression of miR-451a inhibited the expression level of p-AKT1 protein in cells following treatment by MC-LR. These results showed that miR-451a may protect from MC-LR-induced DNA damage by down-regulating the expression of p-AKT1, which provides new clues for the diagnosis and therapy policies for liver damage induced by MC-LR.

Keywords: AKT1; DNA damage; miR-451a; microcystin-LR.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line
DNA Damage*
Humans
Marine Toxins
MicroRNAs*
Microcystins / toxicity*
Proto-Oncogene Proteins c-akt / genetics
Proto-Oncogene Proteins c-akt / metabolism

Substances

MIRN451 microRNA, human
Marine Toxins
MicroRNAs
Microcystins
AKT1 protein, human
Proto-Oncogene Proteins c-akt
cyanoginosin LR