Identification of chondroitin polymerizing factor (CHPF) as tumor promotor in cholangiocarcinoma through regulating cell proliferation, cell apoptosis and cell migration

Cell Cycle. 2021 Mar-Mar;20(5-6):591-602. doi: 10.1080/15384101.2021.1890951. Epub 2021 Mar 2.

Abstract

Cholangiocarcinoma (CCA) is a variety of biliary epithelial tumors involving intrahepatic, perihilar and distal bile duct. It is the most common malignant bile duct tumor in the liver and the second most common primary liver cancer, whose molecular mechanism not fully understood. Specifically, the relationship between CCA and chondroitin polymerizing factor (CHPF) is still not clear. In this study, detection of clinical specimens was performed to preliminarily study the role of CHPF in CCA. CCA cells with CHPF knockdown were constructed for in vitro study, which was also used in the construction of mice xenograft model for investigating the role of CHPF in the development of CCA. The results demonstrated that CHPF was significantly upregulated in CCA tissues compared with normal tissues. High expression of CHPF was correlated with more advanced tumor grade. Moreover, knockdown of CHPF significantly inhibited cell proliferation, cell migration, promoted cell apoptosis and arrest cell cycle in G2 phase in vitro, as well as suppressed tumor growth in vivo. In conclusion, CHPF was identified as a tumor promotor in the development and metastasis of CCA, which may provide a novel therapeutic target for the targeted therapy against CCA.

Keywords: CHPF; Cholangiocarcinoma; cell apoptosis; cell migration; cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Bile Duct Neoplasms / genetics
  • Bile Duct Neoplasms / metabolism*
  • Bile Duct Neoplasms / pathology
  • Carcinogens / metabolism*
  • Cell Line, Tumor
  • Cell Movement / physiology*
  • Cell Proliferation / physiology*
  • Cholangiocarcinoma / genetics
  • Cholangiocarcinoma / metabolism*
  • Cholangiocarcinoma / pathology
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • N-Acetylgalactosaminyltransferases / biosynthesis*
  • N-Acetylgalactosaminyltransferases / genetics

Substances

  • Carcinogens
  • N-Acetylgalactosaminyltransferases
  • chondroitin synthase

Grants and funding

This work was financially supported by Natural Science Foundation of Hunan Province (2019JJ80007 and 2018JJ3294), Key Scientific Research Project of Hunan Provincial Education Department (20B354), and Key Research and Development Project of Hunan Provincial Science and Technology Program (2015sk2050).