The RNA-Binding Protein ELAVL1 Regulates Hepatitis B Virus Replication and Growth of Hepatocellular Carcinoma Cells

被引:8
作者
Kanzaki, Hiroaki [1 ]
Chiba, Tetsuhiro [1 ]
Kaneko, Tatsuya [1 ]
Ao, Junjie [1 ]
Kan, Motoyasu [1 ]
Muroyama, Ryosuke [2 ]
Nakamoto, Shingo [1 ]
Kanda, Tatsuo [3 ]
Maruyama, Hitoshi [4 ]
Kato, Jun [1 ]
Zen, Yoh [5 ]
Kotani, Ai [6 ]
Sekiba, Kazuma [7 ]
Otsuka, Motoyuki [7 ]
Ohtsuka, Masayuki [8 ]
Kato, Naoya [1 ]
机构
[1] Chiba Univ, Grad Sch Med, Dept Gastroenterol, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan
[2] Chiba Univ, Grad Sch Med, Dept Mol Virol, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan
[3] Nihon Univ, Dept Gastroenterol & Hepatol, Sch Med, Itabashi Ku, 30-1 Oyaguchi Kamicho, Tokyo 1738610, Japan
[4] Juntendo Univ, Grad Sch Med, Dept Gastroenterol, Bunkyo Ku, 2-1-1 Hongo, Tokyo 1138421, Japan
[5] Kings Coll Hosp London, Inst Liver Studies, London SE5 9RS, England
[6] Tokai Univ, Inst Med Sci, Div Hematol Malignancy, 143 Shimokasuya, Isehara, Kanagawa 2591193, Japan
[7] Univ Tokyo, Grad Sch Med, Dept Gastroenterol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan
[8] Chiba Univ, Grad Sch Med, Dept Gen Surg, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan
关键词
ELAVL1; HBV; HBx; HCC; RNA-binding protein; ADEFOVIR DIPIVOXIL; HUR EXPRESSION; STABILITY; HBV; DISEASE; CCCDNA;
D O I
10.3390/ijms23147878
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Previous RNA immunoprecipitation followed by proteomic approaches successfully demonstrated that Embryonic Lethal, Abnormal Vision, Drosophila-Like 1 (ELAVL1) interacts with hepatitis B virus (HBV)-derived RNAs. Although ELAVL family proteins stabilize AU-rich element (ARE)-containing mRNAs, their role in HBV transcription remains unclear. This study conducted loss-of-function assays of ELAVL1 for inducible HBV-replicating HepAD38 cells and HBx-overexpressed HepG2 cells. In addition, clinicopathological analyses in primary hepatocellular carcinoma (HCC) surgical samples were also conducted. Lentivirus-mediated short hairpin RNA knockdown of ELAVL1 resulted in a decrease in both viral RNA transcription and production of viral proteins, including HBs and HBx, probably due to RNA stabilization by ELAVL1. Cell growth of HepAD38 cells was more significantly impaired in ELAVL1-knockdown than those in the control group, with or without HBV replication, indicating that ELAVL1 is involved in proliferation by factors other than HBV-derived RNAs. Immunohistochemical analyses of 77 paired HCC surgical specimens demonstrated that diffuse ELAVL1 expression was detected more frequently in HCC tissues (61.0%) than in non-tumor tissues (27.3%). In addition, the abundant expression of ELAVL1 tended to affect postoperative recurrence in HBV-related HCC patients. In conclusion, ELAVL1 contributes not only to HBV replication but also to HCC cell growth. It may be a potent therapeutic target for HBV-related HCC treatment.
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页数:13
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