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NUP153 promotes HCC cells proliferation via c-Myc-mediated downregulation of P15INK4b

  • Caiqin Gan
    Affiliations
    Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430000, China

    Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan 430000, China
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  • Kezhi Zhou
    Affiliations
    Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430000, China

    Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan 430000, China
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  • Mengting Li
    Affiliations
    Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430000, China

    Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan 430000, China
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  • Jian Shang
    Affiliations
    Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430000, China

    Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan 430000, China
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  • Lan Liu
    Correspondence
    Corresponding authors at Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430000, China.
    Affiliations
    Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430000, China

    Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan 430000, China
    Search for articles by this author
  • Qiu Zhao
    Correspondence
    Corresponding authors at Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430000, China.
    Affiliations
    Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430000, China

    Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan 430000, China
    Search for articles by this author
Published:March 11, 2022DOI:https://doi.org/10.1016/j.dld.2022.02.008

      Abstract

      Background and aim

      Nucleoporin NUP153 (NUP153) is involved in the regulation of nuclear transportation, mitosis, and tumor progression in various cancer cells. we aimed to investigate the roles of NUP153 in hepatocellular carcinoma (HCC).

      Methods

      NUP153 expression level and its relationship with clinical prognosis were analyzed based on The Cancer Genome Atlas (TCGA). Quantitative real-time PCR (qRT-PCR), Western Blot (WB), and Immunohistochemistry (IHC) were used to assess NUP153 expression in tissues and cell lines. Loss-of-function experiments were implemented for exploring the roles of NUP153 in HCC cells. Ultimately, how NUP153 exerted biological functions was plumbed by performing rescue assays in HCC.

      Results

      NUP153 expressed highly in HCC tissues and cell lines. Silencing NUP153 inhibited cellular multiplication, G1/S transition, migration, and triggered cytoskeletal rearrangement of Huh7 and HepG2 cells. Knockdown NUP153 caused up-regulation of mRNA and protein levels of P15, and siRNA deprivation of P15 partially reversed the function of low-level NUP153 in HCC. Meanwhile, silencing NUP153 caused down-regulation of mRNA and protein levels of c-Myc. Furthermore, the up-regulation of P15 and cell G1/S phase arrest induced by silencing NUP153 were partially reversed by overexpression of c-Myc.

      Conclusions

      NUP153 increases the proliferation ability of cells via the c-Myc/P15 axis in HCC.

      Keywords

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