Dysregulation of miRNA in chronic hepatitis B is associated with hepatocellular carcinoma risk after nucleos(t)ide analogue treatment
Autor: | Michihiro Suzuki, Hiroyuki Yamamoto, Hideaki Takahashi, S Iwabuchi, Yasushi Sasaki, Masayuki Takagi, Takeshi Niinuma, Hiroshi Yotsuyanagi, Chiaki Okuse, Yasuhito Tanaka, Naoki Matsumoto, Norie Yamada, Ritsuko Oikawa, Takeya Tsutsumi, Takeshi Matsui, Takehito Otsubo, Takashi Tokino, Hideki Wakasugi, Hiromu Suzuki, Noriyuki Akutsu, Hiroshi Nakase, Hajime Sasaki, Yuko Takeba, Shigeru Sasaki, Jong-Hon Kang, Eiichiro Yamamoto, Masayuki Nakano, Yasushi Ariizumi, Masahiro Kai, Hiroshi Kitajima, Fumio Itoh |
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Rok vydání: | 2018 |
Předmět: |
Adult
Male 0301 basic medicine Hepatitis B virus Cancer Research Carcinoma Hepatocellular Guanine Disease medicine.disease_cause Antiviral Agents 03 medical and health sciences Hepatitis B Chronic 0302 clinical medicine Chronic hepatitis Cell Line Tumor microRNA medicine Humans neoplasms Gene Aged business.industry Gene Expression Profiling Tumor Suppressor Proteins Incidence (epidemiology) Liver Neoplasms Hep G2 Cells Middle Aged medicine.disease Cyclin-Dependent Kinases digestive system diseases Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology Oncology 030220 oncology & carcinogenesis Hepatocellular carcinoma Cancer research Female Cyclin-dependent kinase 7 Carrier Proteins business Cyclin-Dependent Kinase-Activating Kinase |
Zdroj: | Cancer Letters. 434:91-100 |
ISSN: | 0304-3835 |
DOI: | 10.1016/j.canlet.2018.07.019 |
Popis: | Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC). Nucleos(t)ide analogue (NA) therapy effectively reduces the incidence of HCC, but it does not completely prevent the disease. Here, we show that dysregulation of microRNAs (miRNAs) is involved in post-NA HCC development. We divided chronic hepatitis B (CHB) patients who received NA therapy into two groups: 1) those who did not develop HCC during the follow-up period after NA therapy (no-HCC group) and 2) those who did (HCC group). miRNA expression profiles were significantly altered in CHB tissues as compared to normal liver, and the HCC group showed greater alteration than the no-HCC group. NA treatment restored the miRNA expression profiles to near-normal in the no-HCC group, but it was less effective in the HCC group. A number of miRNAs implicated in HCC, including miR-101, miR-140, miR-152, miR-199a-3p, and let-7g, were downregulated in CHB. Moreover, we identified CDK7 and TACC2 as novel target genes of miR-199a-3p. Our results suggest that altered miRNA expression in CHB contributes to HCC development, and that improvement of miRNA expression after NA treatment is associated with reduced HCC risk. |
Databáze: | OpenAIRE |
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