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

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 r...

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Autores principales: Kanzaki, Hiroaki, Chiba, Tetsuhiro, Kaneko, Tatsuya, Ao, Junjie, Kan, Motoyasu, Muroyama, Ryosuke, Nakamoto, Shingo, Kanda, Tatsuo, Maruyama, Hitoshi, Kato, Jun, Zen, Yoh, Kotani, Ai, Sekiba, Kazuma, Otsuka, Motoyuki, Ohtsuka, Masayuki, Kato, Naoya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316910/
https://www.ncbi.nlm.nih.gov/pubmed/35887229
http://dx.doi.org/10.3390/ijms23147878
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author Kanzaki, Hiroaki
Chiba, Tetsuhiro
Kaneko, Tatsuya
Ao, Junjie
Kan, Motoyasu
Muroyama, Ryosuke
Nakamoto, Shingo
Kanda, Tatsuo
Maruyama, Hitoshi
Kato, Jun
Zen, Yoh
Kotani, Ai
Sekiba, Kazuma
Otsuka, Motoyuki
Ohtsuka, Masayuki
Kato, Naoya
author_facet Kanzaki, Hiroaki
Chiba, Tetsuhiro
Kaneko, Tatsuya
Ao, Junjie
Kan, Motoyasu
Muroyama, Ryosuke
Nakamoto, Shingo
Kanda, Tatsuo
Maruyama, Hitoshi
Kato, Jun
Zen, Yoh
Kotani, Ai
Sekiba, Kazuma
Otsuka, Motoyuki
Ohtsuka, Masayuki
Kato, Naoya
author_sort Kanzaki, Hiroaki
collection PubMed
description 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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spelling pubmed-93169102022-07-27 The RNA-Binding Protein ELAVL1 Regulates Hepatitis B Virus Replication and Growth of Hepatocellular Carcinoma Cells Kanzaki, Hiroaki Chiba, Tetsuhiro Kaneko, Tatsuya Ao, Junjie Kan, Motoyasu Muroyama, Ryosuke Nakamoto, Shingo Kanda, Tatsuo Maruyama, Hitoshi Kato, Jun Zen, Yoh Kotani, Ai Sekiba, Kazuma Otsuka, Motoyuki Ohtsuka, Masayuki Kato, Naoya Int J Mol Sci Article 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. MDPI 2022-07-17 /pmc/articles/PMC9316910/ /pubmed/35887229 http://dx.doi.org/10.3390/ijms23147878 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kanzaki, Hiroaki
Chiba, Tetsuhiro
Kaneko, Tatsuya
Ao, Junjie
Kan, Motoyasu
Muroyama, Ryosuke
Nakamoto, Shingo
Kanda, Tatsuo
Maruyama, Hitoshi
Kato, Jun
Zen, Yoh
Kotani, Ai
Sekiba, Kazuma
Otsuka, Motoyuki
Ohtsuka, Masayuki
Kato, Naoya
The RNA-Binding Protein ELAVL1 Regulates Hepatitis B Virus Replication and Growth of Hepatocellular Carcinoma Cells
title The RNA-Binding Protein ELAVL1 Regulates Hepatitis B Virus Replication and Growth of Hepatocellular Carcinoma Cells
title_full The RNA-Binding Protein ELAVL1 Regulates Hepatitis B Virus Replication and Growth of Hepatocellular Carcinoma Cells
title_fullStr The RNA-Binding Protein ELAVL1 Regulates Hepatitis B Virus Replication and Growth of Hepatocellular Carcinoma Cells
title_full_unstemmed The RNA-Binding Protein ELAVL1 Regulates Hepatitis B Virus Replication and Growth of Hepatocellular Carcinoma Cells
title_short The RNA-Binding Protein ELAVL1 Regulates Hepatitis B Virus Replication and Growth of Hepatocellular Carcinoma Cells
title_sort rna-binding protein elavl1 regulates hepatitis b virus replication and growth of hepatocellular carcinoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316910/
https://www.ncbi.nlm.nih.gov/pubmed/35887229
http://dx.doi.org/10.3390/ijms23147878
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