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.
发表日期:2024 Jul 15
作者:
Xie Xing, Conghui Wang, Sangsang Tang, Qian Yang, Zhangjin Shen, Jiawei Zhu, Xiaodong Cheng, Xinyu Wang, Xing Xie, Junfen Xu, Weiguo Lu
来源:
Cellular & Molecular Immunology
摘要:
长链非编码RNA(lncRNA)在卵巢癌(OC)的发生、发展中发挥着不可或缺的作用。然而,lncRNA 在 OC 进展中的潜在作用尚不清楚。为了研究RAD51同源物B-反义1(RAD51B-AS1)(一种新型lncRNA)在OC中的详细作用和机制,采用逆转录定量聚合酶链反应(RT-qPCR)来验证RAD51B-AS1的表达。使用细胞计数试剂盒-8 (CCK-8)、集落形成、Transwell 和流式细胞术检测细胞增殖、转移和凋亡。建立小鼠异种移植模型用于检测肿瘤发生。结果显示,RAD51B-AS1 在高度转移的人 OC 细胞系和 OC 组织中显着上调。 RAD51B-AS1显着增加OC细胞的增殖和转移,增强其对失巢凋亡的抵抗力。生物遗传学预测分析显示RAD51B-AS1的唯一靶基因是RAD51B。随后的基因功能实验表明,RAD51B具有与RAD51B-AS1相同的生物学效应。拯救实验表明,体外和体内RAD51B沉默可部分或完全逆转RAD51B-AS1过表达所促进的恶性生物学行为。由此可见,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表达的正向调节有关。 RAD51B-AS1有望作为诊断和预测OC不良预后的新型分子生物标志物,并作为疾病管理的潜在治疗靶点。
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.