Role of microRNA-210-3p in hepatitis B virus-related hepatocellular carcinoma
| Autor: | Akira Nishiyama, Kunitada Shimotohno, Takashi Himoto, Keiichi Okano, Yu Guan, Joji Tani, Kiyoyuki Kobayashi, Tomoko Tadokoro, Asahiro Morishita, Taiga Chiyo, Takako Nomura, Shima Mimura, Tsutomu Masaki, Koji Fujita, Kyoko Oura, Yasuyuki Suzuki, Hideki Kamada, Hisakazu Iwama, Shintaro Fujihara, Hirohito Yoneyama |
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| Rok vydání: | 2020 |
| Předmět: |
Gene Expression Regulation
Viral Male Hepatitis B virus Carcinoma Hepatocellular Physiology Biology Virus Replication medicine.disease_cause Cell Line Tumor Physiology (medical) Hepatitis B virus X protein microRNA medicine Humans Viral Regulatory and Accessory Proteins neoplasms Aged Hepatology Liver Neoplasms Gastroenterology virus diseases Cell Transformation Viral Hepatitis B medicine.disease digestive system diseases Gene Expression Regulation Neoplastic MicroRNAs HBx Hepatocellular carcinoma Host-Pathogen Interactions Trans-Activators Cancer research Female Signal Transduction |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 318:G401-G409 |
| ISSN: | 1522-1547 0193-1857 |
| DOI: | 10.1152/ajpgi.00269.2019 |
| Popis: | Hepatitis B virus (HBV)-related hepatocarcinogenesis is not necessarily associated with the liver fibrotic stage and is occasionally seen at early fibrotic stages. MicroRNAs (miRNAs) are essentially 18- to 22-nucleotide-long endogenous noncoding RNAs. Aberrant miRNA expression is a common feature of various human cancers. The aberrant expression of specific miRNAs has been shown in hepatocellular carcinoma (HCC) tissue compared with nontumor tissue. Thus, we examined targetable miRNAs as a potential new biomarker related to the high risk of HBV-related hepatocarcinogenesis, toward the prevention of cancer-related deaths. HCC tissue samples from 29 patients who underwent hepatectomy at our hospital in 2002–2013 were obtained. We extracted the total RNA and analyzed it by microRNA array, real-time RT-PCR, and three comparisons: 1) HBV-related HCC and adjacent nontumor tissue, 2) HCV-related HCC and adjacent nontumor tissue, and 3) non-HBV-, non-HCV-related HCC and adjacent nontumor tissue. We also performed a functional analysis of miRNAs specific for HBV-related HCC by using HBV-positive HCC cell lines. MiR-210-3p expression was significantly increased only in the HBV-related HCC tissue samples. MiR-210-3p expression was upregulated, and the levels of its target genes were reduced in the HBV-positive HCC cells. The inhibition of miR-210-3p enhanced its target gene expression in the HBV-positive HCC cells. In addition, miR-210-3p regulated the HBx expression in HBV-infected Huh7/NTCP cells. The enhanced expression of miR-210-3p was detected specifically in HBV-related HCC and regulated various target genes, including HBx in the HBV-positive HCC cells. MiR-210-3p might, thus, be a new biomarker for the risk of HBV-related HCC. NEW & NOTEWORTHY Our present study demonstrated that miR-210-3p is the only microRNA with enhanced expression in HBV-related HCC, and the enhanced expression of miR-210-3p upregulates HBx expression. Therefore, miR-210-3p might be a pivotal biomarker of HBV-related hepatocarcinogenesis, and the inhibition of miR-210-3p could prevent inducing hepatocarcinogenesis related to HBV infection. |
| Databáze: | OpenAIRE |
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