RNA Exosome Component EXOSC4 Amplified in Multiple Cancer Types Is Required for the Cancer Cell Survival |
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| Authors: | Kenzui Taniue Tanzina Tanu Yuki Shimoura Shuhei Mitsutomi Han Han Rika Kakisaka Yusuke Ono Nobue Tamamura Kenji Takahashi Youichiro Wada Yusuke Mizukami Nobuyoshi Akimitsu |
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| Affiliation: | 1.Isotope Science Center, The University of Tokyo, Tokyo 113-0032, Japan; (T.T.); (Y.S.); (S.M.); (H.H.); (Y.W.);2.Cancer Genomics and Precision Medicine, Department of Medicine, Asahikawa Medical University, Asahikawa 078-8510, Japan; (N.T.); (K.T.); (Y.M.);3.Institute of Biomedical Research, Sapporo Higashi Tokushukai Hospital, Sapporo 065-0033, Japan; (R.K.); (Y.O.) |
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| Abstract: | 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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| Keywords: | TCGA PanCancer RNA exosome gene amplification EXOSC4 pancreatic cancer cell survival |
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