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RNA Exosome Component EXOSC4 Amplified in Multiple Cancer Types Is Required for the Cancer Cell Survival

The RNA exosome is a multi-subunit ribonuclease complex that is evolutionally conserved and the major cellular machinery for the surveillance, processing, degradation, and turnover of diverse RNAs essential for cell viability. Here we performed integrated genomic and clinicopathological analyses of...

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Autores principales: Taniue, Kenzui, Tanu, Tanzina, Shimoura, Yuki, Mitsutomi, Shuhei, Han, Han, Kakisaka, Rika, Ono, Yusuke, Tamamura, Nobue, Takahashi, Kenji, Wada, Youichiro, Mizukami, Yusuke, Akimitsu, Nobuyoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8745236/
https://www.ncbi.nlm.nih.gov/pubmed/35008922
http://dx.doi.org/10.3390/ijms23010496
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author Taniue, Kenzui
Tanu, Tanzina
Shimoura, Yuki
Mitsutomi, Shuhei
Han, Han
Kakisaka, Rika
Ono, Yusuke
Tamamura, Nobue
Takahashi, Kenji
Wada, Youichiro
Mizukami, Yusuke
Akimitsu, Nobuyoshi
author_facet Taniue, Kenzui
Tanu, Tanzina
Shimoura, Yuki
Mitsutomi, Shuhei
Han, Han
Kakisaka, Rika
Ono, Yusuke
Tamamura, Nobue
Takahashi, Kenji
Wada, Youichiro
Mizukami, Yusuke
Akimitsu, Nobuyoshi
author_sort Taniue, Kenzui
collection PubMed
description The RNA exosome is a multi-subunit ribonuclease complex that is evolutionally conserved and the major cellular machinery for the surveillance, processing, degradation, and turnover of diverse RNAs essential for cell viability. Here we performed integrated genomic and clinicopathological analyses of 27 RNA exosome components across 32 tumor types using The Cancer Genome Atlas PanCancer Atlas Studies’ datasets. We discovered that the EXOSC4 gene, which encodes a barrel component of the RNA exosome, was amplified across multiple cancer types. We further found that EXOSC4 alteration is associated with a poor prognosis of pancreatic cancer patients. Moreover, we demonstrated that EXOSC4 is required for the survival of pancreatic cancer cells. EXOSC4 also repressed BIK expression and destabilized SESN2 mRNA by promoting its degradation. Furthermore, knockdown of BIK and SESN2 could partially rescue pancreatic cells from the reduction in cell viability caused by EXOSC4 knockdown. Our study provides evidence for EXOSC4-mediated regulation of BIK and SESN2 mRNA in the survival of pancreatic tumor cells.
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spelling pubmed-87452362022-01-11 RNA Exosome Component EXOSC4 Amplified in Multiple Cancer Types Is Required for the Cancer Cell Survival Taniue, Kenzui Tanu, Tanzina Shimoura, Yuki Mitsutomi, Shuhei Han, Han Kakisaka, Rika Ono, Yusuke Tamamura, Nobue Takahashi, Kenji Wada, Youichiro Mizukami, Yusuke Akimitsu, Nobuyoshi Int J Mol Sci Article The RNA exosome is a multi-subunit ribonuclease complex that is evolutionally conserved and the major cellular machinery for the surveillance, processing, degradation, and turnover of diverse RNAs essential for cell viability. Here we performed integrated genomic and clinicopathological analyses of 27 RNA exosome components across 32 tumor types using The Cancer Genome Atlas PanCancer Atlas Studies’ datasets. We discovered that the EXOSC4 gene, which encodes a barrel component of the RNA exosome, was amplified across multiple cancer types. We further found that EXOSC4 alteration is associated with a poor prognosis of pancreatic cancer patients. Moreover, we demonstrated that EXOSC4 is required for the survival of pancreatic cancer cells. EXOSC4 also repressed BIK expression and destabilized SESN2 mRNA by promoting its degradation. Furthermore, knockdown of BIK and SESN2 could partially rescue pancreatic cells from the reduction in cell viability caused by EXOSC4 knockdown. Our study provides evidence for EXOSC4-mediated regulation of BIK and SESN2 mRNA in the survival of pancreatic tumor cells. MDPI 2022-01-02 /pmc/articles/PMC8745236/ /pubmed/35008922 http://dx.doi.org/10.3390/ijms23010496 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
Taniue, Kenzui
Tanu, Tanzina
Shimoura, Yuki
Mitsutomi, Shuhei
Han, Han
Kakisaka, Rika
Ono, Yusuke
Tamamura, Nobue
Takahashi, Kenji
Wada, Youichiro
Mizukami, Yusuke
Akimitsu, Nobuyoshi
RNA Exosome Component EXOSC4 Amplified in Multiple Cancer Types Is Required for the Cancer Cell Survival
title RNA Exosome Component EXOSC4 Amplified in Multiple Cancer Types Is Required for the Cancer Cell Survival
title_full RNA Exosome Component EXOSC4 Amplified in Multiple Cancer Types Is Required for the Cancer Cell Survival
title_fullStr RNA Exosome Component EXOSC4 Amplified in Multiple Cancer Types Is Required for the Cancer Cell Survival
title_full_unstemmed RNA Exosome Component EXOSC4 Amplified in Multiple Cancer Types Is Required for the Cancer Cell Survival
title_short RNA Exosome Component EXOSC4 Amplified in Multiple Cancer Types Is Required for the Cancer Cell Survival
title_sort rna exosome component exosc4 amplified in multiple cancer types is required for the cancer cell survival
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8745236/
https://www.ncbi.nlm.nih.gov/pubmed/35008922
http://dx.doi.org/10.3390/ijms23010496
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