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

doi:10.3390/jpm12020201

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

Aston Medical School

Department of Life Sciences, Division of Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK
Department of Life Sciences, Division of Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK; Division of Thoracic Surgery, The Royal Brompton Harefield NHS Foundation Trust, Harefield Hospital, Harefield UB9 6JH, UK
Division of Thoracic Surgery, The Royal Brompton Harefield NHS Foundation Trust, Harefield Hospital, Harefield UB9 6JH, UK; Department of Oncology and Reconstructive Surgery, Sechenov First Moscow State, Medical University, 119146 Moscow, Russia
Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, CV2 2DX, United Kingdom; Warwick Medical School, University of Warwick, Coventry, CV4 7AL, United Kingdom
Department of Life Sciences, Division of Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK; Mount Vernon Cancer Centre, Northwood, London HA6 2RN, UK

Research output: Contribution to journal › Article › peer-review

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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 language	English
Article number	201
Journal	Journal of Personalized Medicine
Volume	12
Issue number	2
DOIs	https://doi.org/10.3390/jpm12020201
Publication status	Published - 1 Feb 2022

Bibliographical note

© 2022 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

ovarian cancer
RAD51AP1
biomarker
T2DM

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Cite this

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title = "Differential Expression of RAD51AP1 in Ovarian Cancer: Effects of siRNA In Vitro",

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.",

keywords = "ovarian cancer, RAD51AP1, biomarker, T2DM",

author = "Alice Filipe and Periklis Katopodis and Dimple Chudasama and Rachel Kerslake and Jeyarooban Jeyaneethi and Vladimir Anikin and Elisabete Silva and Ioannis Kyrou and Randeva, \{Harpal S.\} and Cristina Sisu and Marcia Hall and Emmanouil Karteris",

note = "{\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). ",

year = "2022",

month = feb,

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AU - Filipe, Alice

AU - Katopodis, Periklis

AU - Chudasama, Dimple

AU - Kerslake, Rachel

AU - Jeyaneethi, Jeyarooban

AU - Anikin, Vladimir

AU - Silva, Elisabete

AU - Kyrou, Ioannis

AU - Randeva, Harpal S.

AU - Sisu, Cristina

AU - Hall, Marcia

AU - Karteris, Emmanouil

N1 - © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

PY - 2022/2/1

Y1 - 2022/2/1

N2 - 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.

AB - 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.

KW - ovarian cancer

KW - RAD51AP1

KW - biomarker

KW - T2DM

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DO - 10.3390/jpm12020201

M3 - Article

SN - 2075-4426

VL - 12

JO - Journal of Personalized Medicine

JF - Journal of Personalized Medicine

IS - 2

M1 - 201

ER -

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

Abstract

Bibliographical note

UN SDGs

Keywords

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