The prolyl hydroxylase OGFOD1 promotes cancer cell proliferation by regulating the expression of cell cycle regulators

FEBS Lett. 2023 Apr;597(8):1073-1085. doi: 10.1002/1873-3468.14547. Epub 2022 Dec 12.

Abstract

OGFOD1, a prolyl-hydroxylase, has been reported to translocate from the nucleus to the cytoplasm in response to cellular stress. Here, we demonstrate that OGFOD1 regulates the transcription and post-transcriptional stabilization of cell cycle-related genes. OGFOD1 knockdown in lung cancer cells induced cell cycle arrest through the specific depletion of cyclin-dependent kinase (CDK) 1, CDK2 and cyclin B1 (CCNB1) mRNAs and the nuclear accumulation of p21Cip1 . Analysis of the mRNA dynamics in these cells revealed that CDK1 decreased in a time-dependent manner, reflecting post-transcriptional regulation by OGFOD1 and the RNA-binding protein HuR. In contrast, the depletion of CDK2 and CCNB1 resulted from decreased transcription mediated by OGFOD1. These results indicate that OGFOD1 is required to maintain the function of specific cell cycle regulators during cancer cell proliferation.

Keywords: CDK; HuR; OGFOD1; cyclin; post-transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Neoplasms*
  • Prolyl Hydroxylases* / metabolism

Substances

  • Prolyl Hydroxylases
  • Cyclin-Dependent Kinase Inhibitor p21