Suppression of optineurin impairs the progression of hepatocellular carcinoma through regulating mitophagy

Autophagy removes damaged organelles to inhibit malignant transformation during tumor initiation. Once a cancer matures, it uses the autophagic pathway as an energy source. Optineurin (OPTN) is an autophagy adaptor protein that recruits microtubule‐associated protein 1 light chain 3, an autophagosom...

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Autores principales: Inokuchi, Shoichi, Yoshizumi, Tomoharu, Toshima, Takeo, Itoh, Shinji, Yugawa, Kyohei, Harada, Noboru, Mori, Hiroyuki, Fukuhara, Takasuke, Matsuura, Yoshiharu, Mori, Masaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940236/
https://www.ncbi.nlm.nih.gov/pubmed/33600074
http://dx.doi.org/10.1002/cam4.3519
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author Inokuchi, Shoichi
Yoshizumi, Tomoharu
Toshima, Takeo
Itoh, Shinji
Yugawa, Kyohei
Harada, Noboru
Mori, Hiroyuki
Fukuhara, Takasuke
Matsuura, Yoshiharu
Mori, Masaki
author_facet Inokuchi, Shoichi
Yoshizumi, Tomoharu
Toshima, Takeo
Itoh, Shinji
Yugawa, Kyohei
Harada, Noboru
Mori, Hiroyuki
Fukuhara, Takasuke
Matsuura, Yoshiharu
Mori, Masaki
author_sort Inokuchi, Shoichi
collection PubMed
description Autophagy removes damaged organelles to inhibit malignant transformation during tumor initiation. Once a cancer matures, it uses the autophagic pathway as an energy source. Optineurin (OPTN) is an autophagy adaptor protein that recruits microtubule‐associated protein 1 light chain 3, an autophagosome marker, to the autophagosome. Despite studies of the relation between cancer progression and autophagy adaptor proteins, there are no reports to our knowledge of a correlation between hepatocellular carcinoma (HCC) and OPTN. We aimed here to investigate the effects of OPTN expression on HCC progression through autophagy. Immunohistochemistry was used to measure the OPTN expression in the tissues of 141 Japanese patients with HCC. The effects of OPTN expression on HCC progression and mitophagy were assessed using an OPTN knockout (KO) cell line in vitro. We used this KO cell line to establish and exploit a mouse model of HCC to determine the effects of OPTN expression on tumor progression. Immunohistochemical analysis showed that patients with elevated expression of OPTN experienced shorter overall survival (OS) and recurrence‐free survival (RFS). OPTN KO cells proliferated relatively slower versus wild‐type (WT) cells in vitro. Western blot analysis showed that mitophagy was suppressed in OPTN KO cells, and ATP synthesis and beta‐oxidation were reduced. The mouse model of HCC showed that OPTN KO cells formed smaller tumors versus WT cells less 10 weeks after implantation. Overall, the present findings suggest that OPTN is a key mediator of mitophagy that contributes to HCC progression through mitochondrial energy production.
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spelling pubmed-79402362021-03-16 Suppression of optineurin impairs the progression of hepatocellular carcinoma through regulating mitophagy Inokuchi, Shoichi Yoshizumi, Tomoharu Toshima, Takeo Itoh, Shinji Yugawa, Kyohei Harada, Noboru Mori, Hiroyuki Fukuhara, Takasuke Matsuura, Yoshiharu Mori, Masaki Cancer Med Clinical Cancer Research Autophagy removes damaged organelles to inhibit malignant transformation during tumor initiation. Once a cancer matures, it uses the autophagic pathway as an energy source. Optineurin (OPTN) is an autophagy adaptor protein that recruits microtubule‐associated protein 1 light chain 3, an autophagosome marker, to the autophagosome. Despite studies of the relation between cancer progression and autophagy adaptor proteins, there are no reports to our knowledge of a correlation between hepatocellular carcinoma (HCC) and OPTN. We aimed here to investigate the effects of OPTN expression on HCC progression through autophagy. Immunohistochemistry was used to measure the OPTN expression in the tissues of 141 Japanese patients with HCC. The effects of OPTN expression on HCC progression and mitophagy were assessed using an OPTN knockout (KO) cell line in vitro. We used this KO cell line to establish and exploit a mouse model of HCC to determine the effects of OPTN expression on tumor progression. Immunohistochemical analysis showed that patients with elevated expression of OPTN experienced shorter overall survival (OS) and recurrence‐free survival (RFS). OPTN KO cells proliferated relatively slower versus wild‐type (WT) cells in vitro. Western blot analysis showed that mitophagy was suppressed in OPTN KO cells, and ATP synthesis and beta‐oxidation were reduced. The mouse model of HCC showed that OPTN KO cells formed smaller tumors versus WT cells less 10 weeks after implantation. Overall, the present findings suggest that OPTN is a key mediator of mitophagy that contributes to HCC progression through mitochondrial energy production. John Wiley and Sons Inc. 2021-02-18 /pmc/articles/PMC7940236/ /pubmed/33600074 http://dx.doi.org/10.1002/cam4.3519 Text en © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Clinical Cancer Research
Inokuchi, Shoichi
Yoshizumi, Tomoharu
Toshima, Takeo
Itoh, Shinji
Yugawa, Kyohei
Harada, Noboru
Mori, Hiroyuki
Fukuhara, Takasuke
Matsuura, Yoshiharu
Mori, Masaki
Suppression of optineurin impairs the progression of hepatocellular carcinoma through regulating mitophagy
title Suppression of optineurin impairs the progression of hepatocellular carcinoma through regulating mitophagy
title_full Suppression of optineurin impairs the progression of hepatocellular carcinoma through regulating mitophagy
title_fullStr Suppression of optineurin impairs the progression of hepatocellular carcinoma through regulating mitophagy
title_full_unstemmed Suppression of optineurin impairs the progression of hepatocellular carcinoma through regulating mitophagy
title_short Suppression of optineurin impairs the progression of hepatocellular carcinoma through regulating mitophagy
title_sort suppression of optineurin impairs the progression of hepatocellular carcinoma through regulating mitophagy
topic Clinical Cancer Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940236/
https://www.ncbi.nlm.nih.gov/pubmed/33600074
http://dx.doi.org/10.1002/cam4.3519
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