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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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Autores principales: Filipe, Alice, Katopodis, Periklis, Chudasama, Dimple, Kerslake, Rachel, Jeyaneethi, Jeyarooban, Anikin, Vladimir, Silva, Elisabete, Kyrou, Ioannis, Randeva, Harpal S., Sisu, Cristina, Hall, Marcia, Karteris, Emmanouil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8876735/
https://www.ncbi.nlm.nih.gov/pubmed/35207688
http://dx.doi.org/10.3390/jpm12020201
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author Filipe, Alice
Katopodis, Periklis
Chudasama, Dimple
Kerslake, Rachel
Jeyaneethi, Jeyarooban
Anikin, Vladimir
Silva, Elisabete
Kyrou, Ioannis
Randeva, Harpal S.
Sisu, Cristina
Hall, Marcia
Karteris, Emmanouil
author_facet Filipe, Alice
Katopodis, Periklis
Chudasama, Dimple
Kerslake, Rachel
Jeyaneethi, Jeyarooban
Anikin, Vladimir
Silva, Elisabete
Kyrou, Ioannis
Randeva, Harpal S.
Sisu, Cristina
Hall, Marcia
Karteris, Emmanouil
author_sort Filipe, Alice
collection PubMed
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 pubmed-88767352022-02-26 Differential Expression of RAD51AP1 in Ovarian Cancer: Effects of siRNA In Vitro Filipe, Alice Katopodis, Periklis Chudasama, Dimple Kerslake, Rachel Jeyaneethi, Jeyarooban Anikin, Vladimir Silva, Elisabete Kyrou, Ioannis Randeva, Harpal S. Sisu, Cristina Hall, Marcia Karteris, Emmanouil J Pers Med Article 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. MDPI 2022-02-01 /pmc/articles/PMC8876735/ /pubmed/35207688 http://dx.doi.org/10.3390/jpm12020201 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Article
Filipe, Alice
Katopodis, Periklis
Chudasama, Dimple
Kerslake, Rachel
Jeyaneethi, Jeyarooban
Anikin, Vladimir
Silva, Elisabete
Kyrou, Ioannis
Randeva, Harpal S.
Sisu, Cristina
Hall, Marcia
Karteris, Emmanouil
Differential Expression of RAD51AP1 in Ovarian Cancer: Effects of siRNA In Vitro
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8876735/
https://www.ncbi.nlm.nih.gov/pubmed/35207688
http://dx.doi.org/10.3390/jpm12020201
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