Lv Wei, Jia Yunlong, Wang Jiali, Duan Yuqing, Wang Xuexiao, Liu Tianxu, Hao Shuwei, Liu Lihua
Department of Tumor Immunotherapy, Fourth Hospital of Hebei Medical University and Hebei Cancer Institute, 050035, Shijiazhuang, China.
Department of Gynecology, Fourth Hospital of Hebei Medical University and Hebei Cancer Institute, 050035, Shijiazhuang, China.
Cell Death Discov. 2022 Feb 11;8(1):60. doi: 10.1038/s41420-022-00825-9.
Epithelial ovarian cancer (EOC) is one of the most frequent and fatal gynecologic malignant tumors resulting in an unsatisfying prognosis. Long non-coding RNAs (lncRNAs) play pivotal roles in the tumorigenesis and progression of EOC. However, the profile of lncRNAs involved in EOC remains to be expanded to further improve clinical treatment strategy. In present study, we identified a novel tumor-suppressive lncRNA small nucleolar RNA host gene 10 (SNHG10) in EOC. Kaplan-Meier analysis and COX proportional hazard progression model showed that low expression of SNHG10 was correlated with a poor prognosis of EOC patients. Overexpressing SNHG10 suppressed the proliferation, colony formation, migration, and invasion of EOC cells. Furthermore, SNHG10 was predicted to sponge miR-200a-3p in EOC cells according to the LncBase v.2 experimental module. Then, the binding of SNHG10 and miR-200a-3p was confirmed by performing quantitative real-time PCR (qRT-PCR) and luciferase reporter assays. RNA immunoprecipitation (RIP) showed that SNHG10 and miR-200a-3p occupied the same Ago2 protein to form an RNA-induced silencing complex (RISC). By overlapping the results from the bioinformatics algorithms, tumor-suppressor bridging integrator-1 (BIN1) was found to be a main downstream target of the SNHG10/miR-200a-3p axis. Low expression of BIN1 in EOC tissues was detected by using immunohistochemistry (IHC). Besides, BIN1 and SNHG10 expression was positively correlated in EOC tissues. By performing miRNA rescue experiments, a SNHG10/miR-200a-3p/BIN1 axis and its promoting effects on malignant behaviors and epithelial-mesenchymal transition (EMT) process were verified in EOC cells. Moreover, SNHG10 overexpression significantly suppressed the tumorigenesis and EMT of EOC cells in vivo. Altogether, SNHG10 sponges miR-200a-3p to upregulate BIN1 and thereby exerting its tumor-suppressive effects in EOC. Therefore, the SNHG10/miR-200a-3p/BIN1 axis may act as a potential predictive biomarker and therapeutic target for treating EOC.
上皮性卵巢癌(EOC)是最常见且致命的妇科恶性肿瘤之一,其预后不尽人意。长链非编码RNA(lncRNA)在EOC的肿瘤发生和进展中起关键作用。然而,参与EOC的lncRNA谱仍有待扩展,以进一步改善临床治疗策略。在本研究中,我们在EOC中鉴定出一种新的肿瘤抑制性lncRNA小核仁RNA宿主基因10(SNHG10)。Kaplan-Meier分析和COX比例风险进展模型显示,SNHG10低表达与EOC患者的不良预后相关。过表达SNHG10可抑制EOC细胞的增殖、集落形成、迁移和侵袭。此外,根据LncBase v.2实验模块预测,SNHG10在EOC细胞中可吸附miR-200a-3p。随后,通过定量实时PCR(qRT-PCR)和荧光素酶报告基因检测证实了SNHG10与miR-200a-3p的结合。RNA免疫沉淀(RIP)显示,SNHG10和miR-200a-3p与同一AGO2蛋白结合,形成RNA诱导沉默复合体(RISC)。通过生物信息学算法的结果重叠,发现肿瘤抑制桥接整合素-1(BIN1)是SNHG10/miR-200a-3p轴的主要下游靶点。通过免疫组织化学(IHC)检测发现EOC组织中BIN1低表达。此外,EOC组织中BIN1和SNHG10表达呈正相关。通过进行miRNA拯救实验,在EOC细胞中验证了SNHG10/miR-200a-3p/BIN1轴及其对恶性行为和上皮-间质转化(EMT)过程的促进作用。此外,SNHG10过表达在体内显著抑制了EOC细胞的肿瘤发生和EMT。总之,SNHG10吸附miR-200a-3p以上调BIN1,从而在EOC中发挥其肿瘤抑制作用。因此,SNHG10/miR-200a-3p/BIN1轴可能作为治疗EOC的潜在预测生物标志物和治疗靶点。