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

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

doi:10.3390/jpm12020201

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.

Highlights

Double strand breaks (DSBs) are considered one of the most dangerous types of DNA damage, with the subsequent loss of genome integrity potentially leading to cancer.Cells have a functional capacity to respond to such deleterious insults via homologous recombination (HR) DNA repair
Leveraging the available expression data for ovarian cancer (OvCa) from The Cancer Genome Atlas (TCGA) and GTEX projects, we investigated the differential expression pattern of RAD51AP1 in 419 primary and eight recurrent OvCa samples as well as normal ovarian tissue (n = 88)
We have shown potential involvement of mTOR signaling in OvCa, whereas Zhao et al have shown a relationship between RAD51AP1 and in transforming growth factor β (TGF-β)/Smad signaling pathway

Summary

Introduction

Double strand breaks (DSBs) are considered one of the most dangerous types of DNA damage, with the subsequent loss of genome integrity potentially leading to cancer. Cells have a functional capacity to respond to such deleterious insults via homologous recombination (HR) DNA repair. This highly conserved process is critical for reducing the risk of carcinogenesis [1]. Our group published evidence for a novel role of RAD51AP1 in lung and ovarian cancers, with up-regulation of RAD51AP1 in patient tissue and blood samples compared to control samples at mRNA level [3]. RAD51-associated protein 1 (RAD51AP1), an accessory protein to RAD51, is critical for homologous recombination, a key DNA damage response pathway. There was higher expression of RAD51AP1 in OvCa metastatic to lymph nodes compared to primary cancer samples

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