Full Text:   <733>

Summary:  <261>

Suppl. Mater.: 

CLC number: 

On-line Access: 2024-08-27

Received: 2023-10-17

Revision Accepted: 2024-05-08

Crosschecked: 2024-07-17

Cited: 0

Clicked: 1208

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Xinyi WEI

0009-0008-5637-1704

Junfen XU

0000-0002-2377-0775

Weiguo LU

0000-0003-2062-7145

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2024 Vol.25 No.7 P.581-593

http://doi.org/10.1631/jzus.B2300154


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


Author(s):  Xinyi WEI, Conghui WANG, Sangsang TANG, Qian YANG, Zhangjin SHEN, Jiawei ZHU, Xiaodong CHENG, Xinyu WANG, Xing XIE, Junfen XU, Weiguo LU

Affiliation(s):  Women’s Reproductive Health Laboratory of Zhejiang Province, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; more

Corresponding email(s):   xjfzu@zju.edu.cn, lbwg@zju.edu.cn

Key Words:  Ovarian cancer (OC), Long non-coding RNA (LncRNA), Metastasis, Anoikis


Xinyi WEI, Conghui WANG, Sangsang TANG, Qian YANG, Zhangjin SHEN, Jiawei ZHU, Xiaodong CHENG, Xinyu WANG, Xing XIE, Junfen XU, Weiguo LU. RAD51B-AS1 promotes the malignant biological behavior of ovarian cancer through upregulation of RAD51B[J]. Journal of Zhejiang University Science B, 2024, 25(7): 581-593.

@article{title="RAD51B-AS1 promotes the malignant biological behavior of ovarian cancer through upregulation of RAD51B",
author="Xinyi WEI, Conghui WANG, Sangsang TANG, Qian YANG, Zhangjin SHEN, Jiawei ZHU, Xiaodong CHENG, Xinyu WANG, Xing XIE, Junfen XU, Weiguo LU",
journal="Journal of Zhejiang University Science B",
volume="25",
number="7",
pages="581-593",
year="2024",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2300154"
}

%0 Journal Article
%T RAD51B-AS1 promotes the malignant biological behavior of ovarian cancer through upregulation of RAD51B
%A Xinyi WEI
%A Conghui WANG
%A Sangsang TANG
%A Qian YANG
%A Zhangjin SHEN
%A Jiawei ZHU
%A Xiaodong CHENG
%A Xinyu WANG
%A Xing XIE
%A Junfen XU
%A Weiguo LU
%J Journal of Zhejiang University SCIENCE B
%V 25
%N 7
%P 581-593
%@ 1673-1581
%D 2024
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2300154

TY - JOUR
T1 - RAD51B-AS1 promotes the malignant biological behavior of ovarian cancer through upregulation of RAD51B
A1 - Xinyi WEI
A1 - Conghui WANG
A1 - Sangsang TANG
A1 - Qian YANG
A1 - Zhangjin SHEN
A1 - Jiawei ZHU
A1 - Xiaodong CHENG
A1 - Xinyu WANG
A1 - Xing XIE
A1 - Junfen XU
A1 - Weiguo LU
J0 - Journal of Zhejiang University Science B
VL - 25
IS - 7
SP - 581
EP - 593
%@ 1673-1581
Y1 - 2024
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2300154


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 overexpression 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.

RAD51B-AS1通过上调RAD51B促进卵巢癌的恶性生物学行为

韦欣仪1,王聪慧2,汤桑桑2,杨倩2,沈璋瑾1,朱佳伟2,程晓东2,王新宇2,4,谢幸2,许君芬2,5,吕卫国2,3,5
1浙江大学医学院附属妇产科医院浙江省妇女生殖健康实验室, 中国杭州市, 310006
2浙江大学医学院附属妇产科医院妇科肿瘤科, 中国杭州市, 310006
3浙江大学癌症研究院, 中国杭州市, 310058
4浙江大学医学院第一附属医院妇产科, 中国杭州市, 310003
5浙江省妇产疾病临床医学研究中心, 中国杭州市, 310006
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,RAD51BRAD51B-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。

关键词:卵巢癌(OC);长链非编码RNA(LncRNA);转移;失巢凋亡

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]BhanA, SoleimaniM, MandalSS, 2017. Long noncoding RNA and cancer: a new paradigm. Cancer Res, 77(15):3965-3981.

[2]ChenFF, ZhangL, WuJQ, et al., 2018. HCRP-1 regulates EGFR-AKT-BIM-mediated anoikis resistance and serves as a prognostic marker in human colon cancer. Cell Death Dis, 9(12):1176.

[3]ChenLM, YangPP, al HaqAT, et al., 2022. Oligo-Fucoidan supplementation enhances the effect of Olaparib on preventing metastasis and recurrence of triple-negative breast cancer in mice. J Biomed Sci, 29:70.

[4]ChiuWC, FangPT, LeeYC, et al., 2020. DNA repair protein Rad51 induces tumor growth and metastasis in esophageal squamous cell carcinoma via a p38/Akt-dependent pathway. Ann Surg Oncol, 27(6):2090-2101.

[5]CruzC, Castroviejo-BermejoM, Gutiérrez-EnríquezS, et al., 2018. RAD51 foci as a functional biomarker of homologous recombination repair and PARP inhibitor resistance in germline BRCA-mutated breast cancer. Ann Oncol, 29(5):1203-1210.

[6]CuiXY, ZhanJK, LiuYS, 2021. Roles and functions of antisense lncRNA in vascular aging. Ageing Res Rev, 72:101480.

[7]DangW, CaoPF, YanQJ, et al., 2021. IGFBP7-AS1 is a p53-responsive long noncoding RNA downregulated by Epstein-Barr virus that contributes to viral tumorigenesis. Cancer Lett, 523:135-147.

[8]DengSJ, ChenHY, ZengZ, et al., 2019. Nutrient stress-dysregulated antisense lncRNA GLS-AS impairs GLS-mediated metabolism and represses pancreatic cancer progression. Cancer Res, 79(7):1398-1412.

[9]D'YdewalleC, RamosDM, PylesNJ, et al., 2017. The antisense transcript SMN-AS1 regulates SMN expression and is a novel therapeutic target for spinal muscular atrophy. Neuron, 93(1):66-79.

[10]EdiriweeraMK, TennekoonKH, SamarakoonSR, 2019. Role of the PI3K/AKT/mTOR signaling pathway in ovarian cancer: biological and therapeutic significance. Semin Cancer Biol, 59:147-160.

[11]FaghihiMA, WahlestedtC, 2009. Regulatory roles of natural antisense transcripts. Nat Rev Mol Cell Biol, 10(9):637-643.

[12]GibbonsHR, ShaginurovaG, KimLC, et al., 2018. Divergent lncRNA GATA3-AS1 regulates GATA3 transcription in T-helper 2 cells. Front Immunol, 9:2512.

[13]HuangJ, LuoHL, PanH, et al., 2018. Interaction between RAD51 and MCM complex is essential for RAD51 foci forming in colon cancer HCT116 cells. Biochemistry (Mosc), 83(1):69-75.

[14]JinLT, ChunJ, PanCY, et al., 2018. The PLAG1-GDH1 axis promotes anoikis resistance and tumor metastasis through CamKK2-AMPK signaling in LKB1-deficient lung cancer. Mol Cell, 69(1):87-99.e7.

[15]KatayamaS, TomaruY, KasukawaT, et al., 2005. Antisense transcription in the mammalian transcriptome. Science, 309(5740):1564-1566.

[16]LheureuxS, GourleyC, VergoteI, et al., 2019. Epithelial ovarian cancer. Lancet, 393(10177):1240-1253.

[17]LiangHH, YuT, HanY, et al., 2018. LncRNA PTAR promotes EMT and invasion-metastasis in serous ovarian cancer by competitively binding miR-101-3p to regulate ZEB1 expression. Mol Cancer, 17:119.

[18]LiuYJ, BurnessML, Martin-TrevinoR, et al., 2017. RAD51 mediates resistance of cancer stem cells to PARP inhibition in triple-negative breast cancer. Clin Cancer Res, 23(2):514-522.

[19]NirmalaJG, LopusM, 2020. Cell death mechanisms in eukaryotes. Cell Biol Toxicol, 36(2):145-164.

[20]OudenaardenCRL, van de VenRAH, DerksenPWB, 2018. Re-inforcing the cell death army in the fight against breast cancer. J Cell Sci, 131(16):jcs212563.

[21]PanK, XieY, 2020. LncRNA FOXC2-AS1 enhances FOXC2 mRNA stability to promote colorectal cancer progression via activation of Ca2+-FAK signal pathway. Cell Death Dis, 11(6):434.

[22]PaoliP, GiannoniE, ChiarugiP, 2013. Anoikis molecular pathways and its role in cancer progression. Biochim Biophys Acta, 1833(12):3481-3498.

[23]PeiCL, GongXJ, ZhangY, 2020. LncRNA MALAT-1 promotes growth and metastasis of epithelial ovarian cancer via sponging microRNA-22. Am J Transl Res, 12(11):6977-6987.

[24]RevathideviS, MunirajanAK, 2019. Akt in cancer: mediator and more. Semin Cancer Biol, 59:80-91.

[25]ShenXM, WangCH, ZhuHH, et al., 2021. Exosome-mediated transfer of CD44 from high-metastatic ovarian cancer cells promotes migration and invasion of low-metastatic ovarian cancer cells. J Ovarian Res, 14:38.

[26]ShenZJ, GuLK, LiuYW, et al., 2022. PLAA suppresses ovarian cancer metastasis via METTL3-mediated m6A modification of TRPC3 mRNA. Oncogene, 41(35):4145-4158.

[27]StatelloL, GuoCJ, ChenLL, et al., 2021. Gene regulation by long non-coding RNAs and its biological functions. Nat Rev Mol Cell Biol, 22(2):96-118.

[28]SuWJ, XuM, ChenXQ, et al., 2017. Long noncoding RNA ZEB1-AS1 epigenetically regulates the expressions of ZEB1 and downstream molecules in prostate cancer. Mol Cancer, 16:142.

[29]SungH, FerlayJ, SiegelRL, et al., 2021. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 71(3):209-249.

[30]TaferH, HofackerIL, 2008. RNAplex: a fast tool for RNA‍‒RNA interaction search. Bioinformatics, 24(22):2657-2663.

[31]TianH, LianR, LiY, et al., 2020. AKT-induced lncRNA VAL promotes EMT-independent metastasis through diminishing Trim16-dependent vimentin degradation. Nat Commun, 11:5127.

[32]TorreLA, TrabertB, DesantisCE, et al., 2018. Ovarian cancer statistics, 2018. CA Cancer J Clin, 68(4):284-296.

[33]US Preventive Services Task Force, 2018. Screening for Ovarian Cancer: US Preventive Services Task Force Recommendation Statement. JAMA, 319(6):588-594.

[34]WangZY, JiaRX, WangLL, et al., 2022. The emerging roles of Rad51 in cancer and its potential as a therapeutic target. Front Oncol, 12:935593.

[35]WoditschkaS, EvansL, DuchnowskaR, et al., 2014. DNA double-strand break repair genes and oxidative damage in brain metastasis of breast cancer. J Natl Cancer Inst, 106(7):dju145.

[36]WuDD, ChenX, SunKX, et al., 2017. Role of the lncRNA ABHD11-AS1 in the tumorigenesis and progression of epithelial ovarian cancer through targeted regulation of RhoC. Mol Cancer, 164:138.

[37]WuWM, GaoH, LiXF, et al., 2019. LncRNA TPT1-AS1 promotes tumorigenesis and metastasis in epithelial ovarian cancer by inducing TPT1 expression. Cancer Sci, 110(5):1587-1598.

[38]WuYX, GuWQ, HanX, et al., 2021. LncRNA PVT1 promotes the progression of ovarian cancer by activating TGF‍-‍β pathway via miR-148a-3p/AGO1 axis. J Cell Mol Med, 25(17):8229-8243.

[39]XieWW, SunHZ, LiXD, et al., 2021. Ovarian cancer: epigenetics, drug resistance, and progression. Cancer Cell Int, 21:434.

[40]YangJ, PengSP, ZhangKQ, 2021. LncRNA RP11-499E18.1 inhibits proliferation, migration, and epithelial-mesenchymal transition process of ovarian cancer cells by dissociating PAK2-SOX2 interaction. Front Cell Dev Biol, 9:697831.

[41]ZhangCL, ZhuKP, MaXL, 2017. Antisense lncRNA FOXC2-AS1 promotes doxorubicin resistance in osteosarcoma by increasing the expression of FOXC2. Cancer Lett, 396:66-75.

[42]ZhangXM, MaNY, YaoWQ, et al., 2019. RAD51 is a potential marker for prognosis and regulates cell proliferation in pancreatic cancer. Cancer Cell Int, 19:356.

[43]ZhaoL, JiangL, ZhangM, et al., 2021. NF-κB-activated SPRY4-IT1 promotes cancer cell metastasis by downregulating TCEB1 mRNA via Staufen1-mediated mRNA decay. Oncogene, 40(30):4919-4929.

[44]ZhouZZ, DengH, YanW, et al., 2014. AEG-1 promotes anoikis resistance and orientation chemotaxis in hepatocellular carcinoma cells. PLoS ONE, 9(6):e100372.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE