The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Circ-SNX27 sponging miR-375/RPN1 axis contributes to hepatocellular carcinoma progression

  • Chao Zheng (Surgical Department, Wuhan Hospital of Traditional Chinese Medicine) ;
  • Jin Liang (Department of Spleen Stomach Disease and Hepatobiliary Disease, Wuhan Hospital of Traditional Chinese Medicine) ;
  • Shoude Yu (Department of Spleen Stomach Disease and Hepatobiliary Disease, Wuhan Hospital of Traditional Chinese Medicine) ;
  • Hua Xu (Department of Spleen Stomach Disease and Hepatobiliary Disease, Wuhan Hospital of Traditional Chinese Medicine) ;
  • Lin Dai (Department of Spleen Stomach Disease and Hepatobiliary Disease, Wuhan Hospital of Traditional Chinese Medicine) ;
  • Dan Xu (Department of Spleen Stomach Disease and Hepatobiliary Disease, Wuhan Hospital of Traditional Chinese Medicine)
  • Received : 2022.06.08
  • Accepted : 2023.01.02
  • Published : 2023.07.01
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Abstract

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor with high fatality. It has yet to be reported whether circ-SNX27 can affect the progression of HCC. This study attempted to analyze circ-SNX27's precise role and underlying mechanisms in HCC. HCC cell lines and tumor specimens from HCC patients were analyzed using quantitative real-time PCR and Western blotting to quantify the expressions of circ-SNX27, miR-375, and ribophorin I (RPN1). Cell invasion and cell counting kit 8 experiments were conducted for the evaluation of HCC cell invasion and proliferation. Caspase-3 Activity Assay Kit was utilized to gauge the caspase-3 activity. Luciferase reporter and RNA immunoprecipitation assays were executed to ascertain the relationships among miR-375, circ-SNX27, and RPN1. To determine how circ-SNX27 knockdown affects the growth of HCC xenografts in vivo, tumor-bearing mouse models were constructed. Elevated expressions of circ-SNX27 and RPN1 as well as a reduced miR-375 expression were observed among HCC cells and HCC patient tumor specimens. Knocking-down circ-SNX27 in HCC cells abated their proliferative and invasive abilities but raised their caspase-3 activity. Moreover, the poor levels of circ-SNX27 inhibited HCC tumor growth among the mice. Circ-SNX27 enhanced RPN1 by competitively binding with miR-375. Silencing miR-375 in HCC cells promoted their malignant phenotypes. Nonetheless, the promotive effect of miR375 silencing was reversible via the knockdown of circ-SNX27 or RPN1. This research demonstrated that circ-SNX27 accelerated the progression of HCC by modulating the miR-375/RPN1 axis. This is indicative of circ-SNX27's potential as a target for the treatment of HCC.

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References

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