RAD51AP1 promotes progression of ovarian cancer via TGF-β/Smad signalling pathway

J Cell Mol Med. 2021 Feb;25(4):1927-1938. doi: 10.1111/jcmm.15877. Epub 2020 Dec 13.


Ovarian cancer (OC) is one of the leading causes of female deaths. However, the molecular pathogenesis of OC has still remained elusive. This study aimed to explore the potential genes associated with the progression of OC. In the current study, 3 data sets of OC were downloaded from the GEO database to identify hub gene. Somatic mutation data obtained from TCGA were used to analyse the mutation. Immune cells were used to estimate effect of the hub gene to the tumour microenvironment. RNA-seq and clinical data of OC patients retrieved from TCGA were used to investigate the diagnostic and prognostic values of hub gene. A series of in vitro assays were performed to indicate the function of hub gene and its possible mechanisms in OC. As a result, RAD51AP1 was found as a hub gene, which expression higher was mainly associated with poor survival in OC patients. Up-regulation of RAD51AP1 was closely associated with mutations. RAD51AP1 up-regulation accompanied by accumulated Th2 cells, but reduced CD4 + T cells and CD8 + T cells. Nomogram demonstrated RAD51AP1 increased the accuracy of the model. Down-regulation of RAD51AP1 suppressed proliferation, migration and invasion capabilities of OC cells in vitro. Additionally, scatter plots showed that RAD51AP1 was positively correlated with genes in TGF-β/Smad pathway. The above-mentioned results were validated by RT-qPCR and Western blotting. In conclusion, up-regulation of RAD51AP1 was closely associated with mutations in OC. RAD51AP1 might represent an indicator for predicting OS of OC patients. Besides, RAD51AP1 might accelerate progression of OC by TGF-β/Smad signalling pathway.

Keywords: RAD51AP1; mutation; ovarian cancer; prognostic; progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor
  • Cell Line, Tumor
  • Computational Biology / methods
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Databases, Genetic
  • Disease Progression
  • Female
  • Gene Expression Profiling
  • Humans
  • Mutation
  • Ovarian Neoplasms / etiology
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Prognosis
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Signal Transduction*
  • Smad Proteins / metabolism*
  • Transcriptome
  • Transforming Growth Factor beta / metabolism*


  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • RAD51AP1 protein, human
  • RNA-Binding Proteins
  • Smad Proteins
  • Transforming Growth Factor beta