CHSY1 is upregulated and acts as tumor promotor in gastric cancer through regulating cell proliferation, apoptosis, and migration

Cell Cycle. 2021 Sep;20(18):1861-1874. doi: 10.1080/15384101.2021.1963553. Epub 2021 Aug 19.

Abstract

Gastric cancer is one of the most frequently diagnosed malignant tumors, with rapid progression and poor prognosis. The role of chondroitin sulfate synthase 1 (CHSY1) in the development and progression of gastric cancer was explored and clarified in this study. The immunohistochemistry analysis of clinical tissue samples as well as data mining of public database showed that CHSY1 was significantly upregulated in gastric cancer and associated with more advanced tumor stage and poorer prognosis. In vitro loss-of-function experiments demonstrated the inhibited cell proliferation, colony formation, cell migration, as well as the promoted cell apoptosis by CHSY1 knockdown. Moreover, recovery of CHSY1 expression could attenuate the regulatory effects induced by CHSY1 knockdown. Correspondingly, gastric cancer cells with CHSY1 knockdown showed reduced tumorigenicity and slower tumor growth in vivo. In conclusion, this study identified CHSY1 as a tumor promotor in gastric cancer, which may be utilized as a novel indicator of patients' prognosis and therapeutic target for developing more effective drug for GC treatment.

Keywords: CHSY1; Gastric cancer; cell apoptosis; cell migration; cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Apoptosis / genetics*
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques / methods
  • Glucuronosyltransferase / genetics
  • Glucuronosyltransferase / metabolism*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Multifunctional Enzymes / genetics
  • Multifunctional Enzymes / metabolism*
  • N-Acetylgalactosaminyltransferases / genetics
  • N-Acetylgalactosaminyltransferases / metabolism*
  • Prognosis
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Transfection / methods
  • Tumor Burden / genetics
  • Up-Regulation / genetics*
  • Xenograft Model Antitumor Assays / methods

Substances

  • Multifunctional Enzymes
  • N-Acetylgalactosaminyltransferases
  • Glucuronosyltransferase
  • CHSY1 protein, human

Grants and funding

This work was financially supported by the Science and Technology Development Project of Jilin Province (20190103091JH and 20180101169JC), National Nature Science Foundation of China(NSFC81902447), and the National Nature Science Foundation Cultivation Projiect of the Second Hospital of Jilin University (KYPY 2018-14).