RAD51B-AS1通过上调Rad51b促进卵巢癌的恶性生物学行为
RAD51B-AS1 promotes the malignant biological behavior of ovarian cancer through upregulation of RAD51B
影响因子:4.90000
分区:医学2区 / 生化与分子生物学2区 生物工程与应用微生物2区 医学：研究与实验2区
发表日期:2024 Jul 15
作者:
Xinyi Wei, Conghui Wang, Sangsang Tang, Qian Yang, Zhangjin Shen, Jiawei Zhu, Xiaodong Cheng, Xinyu Wang, Xing Xie, Junfen Xu, Weiguo Lu
摘要
长的非编码RNA（LNCRNA）在发生卵巢癌（OC）的发生和发育中起着必不可少的作用。但是，LNCRNA在OC进展中的潜在参与在很大程度上是未知的。为了研究RAD51同源性B-抗态1（RAD51B-AS1）的详细作用和机制，OC中的一种新型LNCRNA，进行了逆转录 - 定量聚合酶链反应（RT-QPCR），以验证RAD51B-AS1的表达。使用细胞计数KIT-8（CCK-8），菌落形成，Transwell和流式细胞仪分析检测到细胞增殖，转移和凋亡。建立了小鼠异种移植模型以检测肿瘤发生。结果表明，在高度转移的人类OC细胞系和OC组织中，RAD51B-AS1显着上调。 RAD51B-AS1显着增加了OC细胞的增殖和转移，并增强了对Anoikis的抗性。生物遗传学预测分析表明，RAD51B-AS1的唯一靶基因为RAD51B。随后的基因功能实验表明，RAD51B具有与RAD51B-AS1相同的生物学作用。救援实验表明，由RAD51B-AS1过表达促进的恶性生物学行为通过Rad51b在体外和体内进行了部分或完全逆转。因此，RAD51B-AS1促进OC的恶性生物学行为，并激活蛋白激酶B（AKT）/B细胞淋巴瘤蛋白-2（BCL-2）信号通路，这些作用可能与RAD51B表达的阳性调节有关。 RAD51B-AS1有望成为一种新型的分子生物标志物，用于诊断和预测OC的不良预后，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 ofRAD51 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.