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

Brunel University
Harefield Hospital
Sechenov First Moscow State Medical University
University Hospitals Coventry and Warwickshire NHS Trust
University of Warwick
Aston Medical School
Agricultural University of Athens
Mount Vernon Cancer Centre

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

7 Citations (Scopus)

123 Downloads (Pure)

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
Number of pages	13
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

Copyright: © 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/)

Funder

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.

Funding

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.

Funders
Royal Brompton and Harefield Hospitals Charity
Cancer Treatment and Research Trust
University Hospitals Coventry and Warwickshire NHS Trust
Inman Charity

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Biomarker
Ovarian cancer
RAD51AP1
T2DM

ASJC Scopus subject areas

Medicine (miscellaneous)

Access to Document

10.3390/jpm12020201

PublishedFinal published version, 11.2 MBLicence: CC BY

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 = "Biomarker, Ovarian cancer, RAD51AP1, 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 = "Copyright: {\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,

day = "1",

doi = "10.3390/jpm12020201",

language = "English",

volume = "12",

journal = "Journal of Personalized Medicine",

issn = "2075-4426",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

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TY - JOUR

T1 - Differential Expression of RAD51AP1 in Ovarian Cancer

T2 - Effects of siRNA In Vitro

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 - Copyright: © 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 - Biomarker

KW - Ovarian cancer

KW - RAD51AP1

KW - T2DM

UR - https://www.scopus.com/pages/publications/85124130868

U2 - 10.3390/jpm12020201

DO - 10.3390/jpm12020201

M3 - Article

AN - SCOPUS:85124130868

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

Funder

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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