TY - JOUR
T1 - MicroRNA-3145 as a potential therapeutic target for hepatitis B virus
T2 - inhibition of viral replication via downregulation of HBS and HBX
AU - Muchtar, Amrizal
AU - Onomura, Daichi
AU - Ding, Dan
AU - Nishitsuji, Hironori
AU - Shimotohno, Kunitada
AU - Okada, Shunpei
AU - Ueda, Keiji
AU - Watashi, Koichi
AU - Wakita, Takaji
AU - Iida, Kei
AU - Yoshiyama, Hironori
AU - Iizasa, Hisashi
N1 - Publisher Copyright:
Copyright © 2025 Muchtar, Onomura, Ding, Nishitsuji, Shimotohno, Okada, Ueda, Watashi, Wakita, Iida, Yoshiyama and Iizasa.
PY - 2024
Y1 - 2024
N2 - Current treatments for hepatitis B virus (HBV), such as interferons and nucleic acid analogs, have limitations due to side effects like depression and the development of drug-resistant mutants, highlighting the need for new therapeutic approaches. In this study, we identified microRNA-3145 (miR-3145) as a host-derived miRNA with antiviral activity that is upregulated in primary hepatocytes during HBV infection. The expression of its precursor, pri-miR-3145, increased in response to the the virus infection, and miR-3145 downregulated the hepatitis B virus S (HBS) antigen and hepatitis B virus X (HBX), thereby inhibiting viral replication. The binding site for miR-3145 was located in the HBV polymerase (pol) region, as experimentally confirmed. Moreover, overexpression of HBS and HBX induced pri-miR-3145 expression through endoplasmic reticulum stress. The expression of pri-miR-3145 showed a strong correlation with the Nance–Horan syndrome-like 1 (NHSL1) gene, as it is encoded within an intron of NHSL1, and higher NHSL1 expression in hepatocellular carcinoma patients with HBV infection was associated with better prognosis. These findings suggest that miR-3145-3p, along with small molecules targeting its binding sites, holds promise as a potential therapeutic candidate for HBV treatment.
AB - Current treatments for hepatitis B virus (HBV), such as interferons and nucleic acid analogs, have limitations due to side effects like depression and the development of drug-resistant mutants, highlighting the need for new therapeutic approaches. In this study, we identified microRNA-3145 (miR-3145) as a host-derived miRNA with antiviral activity that is upregulated in primary hepatocytes during HBV infection. The expression of its precursor, pri-miR-3145, increased in response to the the virus infection, and miR-3145 downregulated the hepatitis B virus S (HBS) antigen and hepatitis B virus X (HBX), thereby inhibiting viral replication. The binding site for miR-3145 was located in the HBV polymerase (pol) region, as experimentally confirmed. Moreover, overexpression of HBS and HBX induced pri-miR-3145 expression through endoplasmic reticulum stress. The expression of pri-miR-3145 showed a strong correlation with the Nance–Horan syndrome-like 1 (NHSL1) gene, as it is encoded within an intron of NHSL1, and higher NHSL1 expression in hepatocellular carcinoma patients with HBV infection was associated with better prognosis. These findings suggest that miR-3145-3p, along with small molecules targeting its binding sites, holds promise as a potential therapeutic candidate for HBV treatment.
KW - anti-viral drug
KW - endoplasmic reticulum stress
KW - hepatitis B virus
KW - hepatocellular carcinoma
KW - microRNA
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U2 - 10.3389/fmicb.2024.1499216
DO - 10.3389/fmicb.2024.1499216
M3 - Article
AN - SCOPUS:85215528155
SN - 1664-302X
VL - 15
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
M1 - 1499216
ER -