RAD51B-AS1 promotes the malignant biological behavior of ovarian cancer through upregulation of RAD51B

Xinyi WEI; Conghui WANG; Sangsang TANG; Qian YANG; Zhangjin SHEN; Jiawei ZHU; Xiaodong CHENG; Xinyu WANG; Xing XIE; Junfen XU; Weiguo LU

doi:10.1631/jzus.B2300154

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RAD51B-AS1 promotes the malignant biological behavior of ovarian cancer through upregulation of RAD51B

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Research Article | Updated：2024-07-17

RAD51B-AS1 promotes the malignant biological behavior of ovarian cancer through upregulation of RAD51B
RAD51B-AS1 promotes the malignant biological behavior of ovarian cancer through upregulation of RAD51B
RAD51B-AS1通过上调RAD51B促进卵巢癌的恶性生物学行为
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) Vol. 25, Issue 7, Pages: 581-593(2024)
Affiliations：

1.Women’s Reproductive Health Laboratory of Zhejiang Province, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
2.Department of Gynecologic Oncology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
3.Cancer Center, Zhejiang University, Hangzhou 310058, China
4.Department of Obstetrics and Gynecology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
5.Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou 310006, China
Funds：
DOI：10.1631/jzus.B2300154
CLC：
CSTR：
Published： 15 July 2024 ，

Received： 09 March 2023 ，

Revised： 29 August 2023 ，
Accepted：

Xinyi WEI, Conghui WANG, Sangsang TANG, et al. RAD51B-AS1 promotes the malignant biological behavior of ovarian cancer through upregulation of RAD51B. [J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) 25(7):581-593(2024)
DOI：

Xinyi WEI, Conghui WANG, Sangsang TANG, et al. RAD51B-AS1 promotes the malignant biological behavior of ovarian cancer through upregulation of RAD51B. [J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) 25(7):581-593(2024) DOI： 10.1631/jzus.B2300154.

摘要

长链非编码RNA（lncRNA）在卵巢癌的发生发展中起着不可或缺的作用，但它们在卵巢癌进展中的潜在作用在很大程度上仍是未知。为了研究新型lncRNA RAD51B-AS1在卵巢癌中的具体作用和机制，我们通过逆转录-定量聚合酶链反应实验验证了RAD51B-AS1的表达；使用CCK-8实验、集落形成实验、transwell实验和流式细胞术检测细胞的增殖、转移和凋亡水平；建立小鼠异种移植瘤模型检测肿瘤发生情况。结果显示：RAD51B-AS1在人高转移卵巢癌细胞系和卵巢癌组织中显著上调；同时，RAD51B-AS1显著增强卵巢癌细胞的增殖、转移和抵抗失巢凋亡的能力。生物遗传学预测分析显示，RAD51B-AS1的唯一靶基因为RAD51B。随后的基因功能实验表明，RAD51B与RAD51B-AS1具有相同的生物学效应。体外和体内实验均表明，过表达RAD51B-AS1促进的恶性生物学行为可以通过沉默RAD51B的表达部分或完全逆转。由此可见，RAD51B-AS1可促进卵巢癌的恶性生物学行为，并激活Akt/Bcl-2信号通路，这些作用可能与其正向调节RAD51B的表达有关。RAD51B-AS1有望作为一种新的分子生物标志物，用于卵巢癌不良预后的诊断和预测，并作为疾病管理的潜在治疗靶点。

Abstract

Long non-coding RNAs (lncRNAs) play an indispensable role in the occurrence and development of ovarian cancer (OC). However

the potential involvement of lncRNAs in the progression of OC is largely unknown. To investigate the detailed roles and mechanisms of

RAD51 homolog B-antisense 1 (

RAD51B-AS1

)

a novel lncRNA in OC

reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to verify the expression of

RAD51B-AS1

. Cellular proliferation

metastasis

and apoptosis were detected using the cell counting kit-8 (CCK-8)

colony-formation

transwell

and flow cytometry assays. Mouse xenograft models were established for the detection of tumorigenesis. The results revealed that

RAD51B-AS1

was significantly upregulated in a highly metastatic human OC cell line and OC tissues.

RAD51B-AS1

significantly increased the proliferation and metastasis of OC cells and enhanced their resistance to anoikis. Biogenetics prediction analysis revealed that the only target gene of

RAD51B-AS1

was

RAD51B

. Subsequent gene function experiments revealed that

RAD51B

exerts the same biological effects as

RAD51B-AS1

. Rescue experiments demonstrated that the malignant biological behaviors promoted by

RAD51B-AS1

overexp

ression were partially or completely reversed by

RAD51B

silencing in vitro and in vivo. Thus

RAD51B-AS1

promotes the malignant biological behaviors of OC and activates the protein kinase B (Akt)/B cell lymphoma protein-2 (Bcl-2) signaling pathway

and these effects may be associated with the positive regulation of

RAD51B

expression.

RAD51B-AS1

is expected to serve as a novel molecular biomarker for the diagnosis and prediction of poor prognosis in OC

and as a potential therapeutic target for disease management.

关键词

卵巢癌（OC）长链非编码RNA（LncRNA）转移失巢凋亡

Keywords

Ovarian cancer (OC)Long non-coding RNA (LncRNA)MetastasisAnoikis

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