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
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影响因子:4.9
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
DOI:
10.1631/jzus.B2300154
摘要
长链非编码RNA（lncRNAs）在卵巢癌（OC）的发生发展中发挥着不可或缺的作用。然而，lncRNAs在OC进展中的潜在作用尚未被充分研究。为了探究新型lncRNA RAD51B-反义RNA1（RAD51B-AS1）在OC中的具体作用和机制，采用逆转录-定量聚合酶链反应（RT-qPCR）检测RAD51B-AS1的表达水平。在细胞增殖、迁移和凋亡方面，采用细胞计数试剂盒-8（CCK-8）、克隆形成、Transwell迁移和流式细胞术进行检测。建立小鼠异种移植模型以观察肿瘤发生情况。结果显示，RAD51B-AS1在高度转移性的人类OC细胞系和OC组织中显著上调。RAD51B-AS1显著促进OC细胞的增殖和转移，并增强其抗凋亡能力。生物信息预测分析显示，RAD51B是唯一的靶基因。后续功能实验表明，RAD51B具有与RAD51B-AS1相似的生物学效应。拯救实验表明，RAD51B的沉默在体内外能部分或完全逆转RAD51B-AS1过表达所促进的恶性生物行为。因此，RAD51B-AS1促进OC的恶性行为，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表达的正向调控有关。RAD51B-AS1有望作为一种新型分子生物标志物，用于OC的诊断和预后预测，以及潜在的疾病治疗靶点。
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.