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

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 ca...

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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:Journal of Personalized Medicine
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Online Access:https://www.mdpi.com/2075-4426/12/2/201
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author 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
author_facet 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
author_sort Alice Filipe
collection DOAJ
description 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.
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spelling doaj.art-8e3e52cf903f4dbc8d01e191510f78572023-11-23T20:39:47ZengMDPI AGJournal of Personalized Medicine2075-44262022-02-0112220110.3390/jpm12020201Differential Expression of RAD51AP1 in Ovarian Cancer: Effects of siRNA In VitroAlice Filipe0Periklis Katopodis1Dimple Chudasama2Rachel Kerslake3Jeyarooban Jeyaneethi4Vladimir Anikin5Elisabete Silva6Ioannis Kyrou7Harpal S. Randeva8Cristina Sisu9Marcia Hall10Emmanouil Karteris11Department of Life Sciences, Division of Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UKDepartment of Life Sciences, Division of Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UKDepartment of Life Sciences, Division of Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UKDepartment of Life Sciences, Division of Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UKDepartment of Life Sciences, Division of Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UKDivision of Thoracic Surgery, The Royal Brompton & Harefield NHS Foundation Trust, Harefield Hospital, Harefield UB9 6JH, UKDepartment of Life Sciences, Division of Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UKWarwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UKWarwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UKDepartment of Life Sciences, Division of Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UKDepartment of Life Sciences, Division of Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UKDepartment of Life Sciences, Division of Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UKBackground: 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.https://www.mdpi.com/2075-4426/12/2/201ovarian cancerRAD51AP1biomarkerT2DM
spellingShingle 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
Differential Expression of RAD51AP1 in Ovarian Cancer: Effects of siRNA In Vitro
Journal of Personalized Medicine
ovarian cancer
RAD51AP1
biomarker
T2DM
title Differential Expression of RAD51AP1 in Ovarian Cancer: Effects of siRNA In Vitro
title_full Differential Expression of RAD51AP1 in Ovarian Cancer: Effects of siRNA In Vitro
title_fullStr Differential Expression of RAD51AP1 in Ovarian Cancer: Effects of siRNA In Vitro
title_full_unstemmed Differential Expression of RAD51AP1 in Ovarian Cancer: Effects of siRNA In Vitro
title_short Differential Expression of RAD51AP1 in Ovarian Cancer: Effects of siRNA In Vitro
title_sort differential expression of rad51ap1 in ovarian cancer effects of sirna in vitro
topic ovarian cancer
RAD51AP1
biomarker
T2DM
url https://www.mdpi.com/2075-4426/12/2/201
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