Role of microRNA-210-3p in hepatitis B virus-related hepatocellular carcinoma

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 318; no. 3; pp. G401 - G409
• Main Authors: Morishita, Asahiro, Fujita, Koji, Iwama, Hisakazu, Chiyo, Taiga, Fujihara, Shintaro, Oura, Kyoko, Tadokoro, Tomoko, Mimura, Shima, Nomura, Takako, Tani, Joji, Yoneyama, Hirohito, Kobayashi, Kiyoyuki, Kamada, Hideki, Guan, Yu, Nishiyama, Akira, Okano, Keiichi, Suzuki, Yasuyuki, Himoto, Takashi, Shimotohno, Kunitada, Masaki, Tsutomu
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.03.2020
• Subjects: Biomarkers; Chromosome 3; Gene expression; Hepatectomy; Hepatitis; Hepatitis B; Hepatocellular carcinoma; Liver cancer; MicroRNAs; miRNA; Polymerase chain reaction; hepatitis B virus X protein; hepatitis B virus-related hepatocellular carcinoma; microRNA; hepatocarcinogenesis; hepatitis B virus
• ISSN: 0193-1857; 1522-1547; 1522-1547
• DOI: 10.1152/ajpgi.00269.2019

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.