Knockdown CYP2S1 inhibits lung cancer cells proliferation and migration

Cancer Biomark. 2021;32(4):531-539. doi: 10.3233/CBM-210189.

Abstract

Background: The incidence of lung cancer in Yunnan area ranks firstly in the world and underlying molecular mechanisms of lung cancer in Yunnan region are still unclear. We screened a novel potential oncogene CYP2S1 used mRNA microassay and bioinformation database. The function of CYP2S1 in lung cancer has not been reported.

Objective: To investigate the functions of CYP2S1 in lung cancer.

Methods: Immunohistochemistry and Real-time PCR were used to verify the expression of CYP2S1. Colony formation and Transwell assays were used to determine cell proliferation, invasion and migration. Xenograft assays were used to detected cell growth in vivo.

Results: CYP2S1 is significantly up-regulated in lung cancer tissues and cells. Knockdown CYP2S1 in lung cancer cells resulted in decrease cell proliferation, invasion and migration in vitro. Animal experiments showed downregulation of CYP2S1 inhibited lung cancer cell growth in vivo. GSEA analysis suggested that CYP2S1 played functions by regulating E2F targets and G2M checkpoint pathway which involved in cell cycle. Kaplan-Meier analysis indicated that patients with high CYP2S1 had markedly shorter event overall survival (OS) time.

Conclusions: Our data demonstrate that CYP2S1 exerts tumor suppressor function in lung cancer. The high expression of CYP2S1 is an unfavorable prognostic marker for patient survival.

Keywords: CYP2S1; invasion; lung cancer proliferation; migration.

MeSH terms

  • A549 Cells
  • Adenocarcinoma of Lung / enzymology*
  • Adenocarcinoma of Lung / pathology
  • Animals
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Cytochrome P-450 Enzyme System / metabolism*
  • Female
  • Heterografts
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness
  • Up-Regulation

Substances

  • Cytochrome P-450 Enzyme System
  • CYP2S1 protein, human