PSMC2/CCND1 axis promotes development of ovarian cancer through regulating cell growth, apoptosis and migration

Cell Death Dis. 2021 Jul 22;12(8):730. doi: 10.1038/s41419-021-03981-5.

Abstract

Ovarian cancer is known as one of the most common malignancies of the gynecological system, whose treatment is still not satisfactory because of the unclear understanding of molecular mechanism. PSMC2 is an essential component of 19 S regulatory granules in 26 S proteasome and its relationship with ovarian cancer is still not clear. In this study, we found that PSMC2 was upregulated in ovarian cancer tissues, associated with tumor grade and could probably predict poor prognosis. Knocking down the endogenous PSMC2 expression in ovarian cancer cells could decrease colony formation ability, cell motility and cell proliferation rate, along with increasing cell apoptosis rate. Cells models or xenografts formed by cells with relatively lower expression of PSMC2 exhibited weaker oncogenicity and slower growth rate in vivo. Moreover, gene microarray was used to analyze the alteration of gene expression profiling of ovarian cancer induced by PSMC2 knockdown and identify CCND1 as a potential downstream of PSMC2. Further study revealed the mutual regulation between PSMC2 and CCND1, and demonstrated that knockdown of CCND1 could enhance the regulatory effects induced by PSMC2 knockdown and overexpression of CCND1 reverses it. In summary, PSMC2 may promote the development of ovarian cancer through CCND1, which may predict poor prognosis of ovarian cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / genetics
  • ATPases Associated with Diverse Cellular Activities / metabolism*
  • Animals
  • Apoptosis*
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism*
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology*
  • Prognosis
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction*
  • Up-Regulation / genetics

Substances

  • CCND1 protein, human
  • Cyclin D1
  • PSMC2 protein, human
  • Proto-Oncogene Proteins c-akt
  • Proteasome Endopeptidase Complex
  • ATPases Associated with Diverse Cellular Activities