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ARTICLE
RPA3 is transcriptionally activated by YY1 and its depletion enhances radiosensitivity of triple-negative and HER2-positive breast cancer
YANFEI LI1, LULU DAI2, KE CAI2, YINGKUI SONG2, XIQING LIU3,*
1 Clinical Laboratory, Laiyang Central Hospital of Yantai, Laiyang, 265200, China
2 Department of General Surgery, The Eighth People’s Hospital of Qindao, Qingdao, 266000, China
3 Hepatobiliary Surgery, Anqiu People’s Hospital, Anqiu, 262100, China
* Address correspondence to: Xiqing Liu,
BIOCELL 2021, 45(3), 685-694. https://doi.org/10.32604/biocell.2021.013612
Received 13 August 2020; Accepted 03 December 2020; Issue published 03 March 2021
Abstract
RPA3 (Replication Protein A3) (14 kD) is a part of the canonical heterotrimeric replication protein A complex
(RPA/RP-A). This study aimed to explore the functional role of RPA3 and the mechanisms of its dysregulation in breast
cancer. Data from the Cancer Genome Atlas (TCGA)-breast cancer patients and GSE75688 were utilized for gene
expression and survival analysis. Breast cancer cell lines MDA-MB-231 and SK-BR-3 were used for in-vitro cell
studies. Clonogenic assay and immunofluorescent staining of γ-H2AX were performed to examine radiation-induced
cytotoxicity. Systemic correlation analysis was performed to identify potential transcription factors (TFs) regulating
RPA3 expression. ChIP-qPCR and dual-luciferase assay were conducted to verify the transcriptional activating effect
of YY1 on RPA3 expression. Bioinformatic analysis showed that RPA3 expression was upregulated in breast cancer.
Its upregulation was associated with poor survival of basal-like and HER2+ cases. RPA3 inhibition by siRNA reduced
colony formation and increased γ-H2AX foci formation after irradiation in MDA-MB-231 and SK-BR-3 cells. RPA3
expression was transcriptionally activated by YY1 via promoter binding in the two cell lines. Both RPA3 and YY1
expression were positively correlated with their gene-level copy numbers. RPA3 might serve as a potential target for
radio-sensitization in basal-like and HER2+ breast cancer.
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Cite This Article
APA Style
LI, Y., DAI, L., CAI, K., SONG, Y., LIU, X. (2021). RPA3 is transcriptionally activated by YY1 and its depletion enhances radiosensitivity of triple-negative and her2-positive breast cancer. BIOCELL, 45(3), 685-694. https://doi.org/10.32604/biocell.2021.013612
Vancouver Style
LI Y, DAI L, CAI K, SONG Y, LIU X. RPA3 is transcriptionally activated by YY1 and its depletion enhances radiosensitivity of triple-negative and her2-positive breast cancer. BIOCELL . 2021;45(3):685-694 https://doi.org/10.32604/biocell.2021.013612
IEEE Style
Y. LI, L. DAI, K. CAI, Y. SONG, and X. LIU "RPA3 is transcriptionally activated by YY1 and its depletion enhances radiosensitivity of triple-negative and HER2-positive breast cancer," BIOCELL , vol. 45, no. 3, pp. 685-694. 2021. https://doi.org/10.32604/biocell.2021.013612