title: MiR-192 inhibits nucleotide excision repair by targeting ERCC3 and ERCC4 in HepG2.2.15 cells.
abstract: Deficient DNA repair capacity is associated with genetic lesions accumulation and susceptibility to carcinogenesis. MicroRNAs (miRNAs) are small non-coding RNAs that regulate various cellular pathways including DNA repair. Here we hypothesized that the existence of HBV products may interfere with cellular nucleotide excision repair (NER) through microRNA-mediated gene regulation. We found that NER was impaired in HepG2.2.15 cells, a stable HBV-expressing cell line, compared with its parental cell line HepG2. Altered miRNA expression profile, in particular the significant upregulation of miR-192, was observed in HepG2.2.15 cells. Additionally, ERCC3 and ERCC4, two key factors implicated in NER, were identified as targets of miR-192 and over-expressing miR-192 significantly inhibited cellular NER. These results indicated that persistent HBV infection might trigger NER impairment in part through upregulation of miR-192, which suppressed the levels of ERCC3 and ERCC4. It provides new insight into the effect of chronic HBV infection on NER and genetic instability in cancer.
authors.affiliation: Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Qiong-Hui
authors.initials: QH
authors.lastname: Xie
authors.forename: Xing-Xing
authors.initials: XX
authors.lastname: He
authors.forename: Ying
authors.initials: Y
authors.lastname: Chang
authors.forename: Shu-zhen
authors.initials: SZ
authors.lastname: Sun
authors.forename: Xiang
authors.initials: X
authors.lastname: Jiang
authors.forename: Pei-Yuan
authors.initials: PY
authors.lastname: Li
authors.forename: Ju-Sheng
authors.initials: JS
authors.lastname: Lin
mesh_terms: D045744:Cell Line, Tumor; D004265:DNA Helicases / Q000235:genetics*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D042822:Genomic Instability; D006367:HeLa Cells; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; C546783:MIRN192 microRNA, human; D035683:MicroRNAs; C095888:xeroderma pigmentosum group F protein; C072022:XPBC-ERCC-3 protein; D004265:DNA Helicases