Differential Expression of RAD51AP1 in Ovarian Cancer: Effects of siRNA In Vitro

Alice Filipe, Periklis Katopodis, Dimple Chudasama, Rachel Kerslake, Jeyarooban Jeyaneethi, Vladimir Anikin, Elisabete Silva, Ioannis Kyrou, Harpal S. Randeva, Cristina Sisu, Marcia Hall*, Emmanouil Karteris

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: DNA double strand breaks can affect genome integrity potentially leading to cancer. RAD51-associated protein 1 (RAD51AP1), an accessory protein to RAD51, is critical for homologous recombination, a key DNA damage response pathway. Emerging studies indicate a novel role for RAD51AP1 in carcinogenesis. Here we provide additional insight into the role of RAD51AP1 in ovarian cancer (OvCa). Methods: Gene expression and patient phenotype data were obtained from TCGA and GTEX project consortia for bioinformatics analysis. Immunohistochemistry of OvCa tissue microarray was undertaken. Functional analyses were performed in a SKOV3 OvCa cell line with down-regulation of RAD51AP1 using siRNA. Results: RAD51AP1 is overexpressed at gene level in primary and recurrent OvCa compared to controls. At protein level, RAD51AP1 was up-regulated in low grade serous tumors compared to high grade OvCa. There was higher expression of RAD51AP1 in OvCa metastatic to lymph nodes compared to primary cancer samples. Gene enrichment analyses identified 12 differentially expressed genes (DEGs) related to OvCa, eight of which are also common in tissue from patients with type 2 diabetes mellitus (T2DM). Conclusions: RAD51AP1 is overexpressed in OvCa, Given the link between OvCa and T2DM, the eight-gene signature shows potential for predictive value.

Original languageEnglish
Article number201
JournalJournal of Personalized Medicine
Volume12
Issue number2
DOIs
Publication statusPublished - Feb 2022
Externally publishedYes

Bibliographical note

Funding Information:
Funding: This research was funded by Royal Brompton and Harefield Hospitals Charity, Cancer Treatment and Research Trust (CTRT), University Hospitals Coventry and Warwickshire NHS Trust and Inman Charity.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Biomarker
  • Ovarian cancer
  • RAD51AP1
  • T2DM

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