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Molecular Carcinogenesis

Molecular Carcinogenesis

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DSN1 Interaction With Centromere‐Associated Proteins Promotes Chromosomal Instability in Hepatocellular Carcinoma

Published:19 November 2024 DOI: 10.1002/mc.23845 PMID: 39560395
Hongrui Zhou, Mengxue Zhang, Jiabing Lian, Ruichang Wang, Zhe Yang, Jin Wang, Xiuli Bi

Abstract

Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer. Dosage suppressor of NNF1 (DSN1), a component of the MIS12 kinetochore complex, encodes a kinetochore protein crucial for proper mitotic assembly. The role of DSN1 in HCC remains to be elucidated. In this study, we utilized The Cancer Genome Atlas, the Hepatocellular carcinoma Cell Database, and other databases to analyze DSN1 expression and prognosis in samples from patients with HCC. We investigated the signaling pathways regulated by DSN1 and their implications in HCC. Additionally, we engineered siRNAsiRNA/shRNA/shRNA and overexpression vectors for DSN1 and assessed the specific mechanisms of regulatory pathways of DSN1 in hepatoma cell lines and subcutaneous tumor xenograft model. Our findings revealed that DSN1 expression was significantly upregulated in patients with HCC, correlating with decreased survival rates. Elevated DSN1 expression led to the overproduction of cell cycle-related proteins through direct interaction with Centromere Protein T. This interaction contributes to chromosomal instability in patients with HCC, resulting in an aberrant cell cycle and fostering the development and progression of HCC. Increased DSN1 expression is pivotal in HCC initiation and progression. Investigating DSN1 offers valuable insights into the pathogenesis, treatment, and prevention of HCC.

Substances (2)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Colchicine 64-86-8 C22H25NO6 722 suppliers $16.00-$3980.00
4',6-Diamidino-2-phenylindole dihydrochloride 28718-90-3 C16H16ClN5 295 suppliers $14.10-$4800.00

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