Yan Changsheng, Jiang Yi, Wan Yicong, Zhang Lin, Liu Jinhui, Zhou Shulin, Cheng Wenjun
Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University.
Department of Obstetrics and Gynecology, Zhongda Hospital Affiliated to Southeast University, Medical School, Southeast University, Nanjing, Jiangsu, People's Republic of China.
Onco Targets Ther. 2017 Apr 6;10:1993-2002. doi: 10.2147/OTT.S124645. eCollection 2017.
Long noncoding RNA (lncRNA) has been proven to be involved in many biological processes in ovarian cancer (OC). However, the mechanism still remains unknown. In this study, we screened significantly downregulated NBAT-1, which has been proven to play a significant role in breast cancer, clear cell renal cell carcinoma, and neuroblastoma, but not in OC, in two independent datasets with relatively more samples (GSE18520 and GSE38666) from Gene Expression Omnibus. We found that lncRNA NBAT-1 was obviously downregulated in OC tissue compared to normal ovarian tissue (<0.001) which was free of OC, and the detected levels of NBAT-1 were associated with the International Federation of Gynecology and Obstetrics stage and tumor size guidelines. Moreover, it has been shown that lower levels of NBAT-1 predict poor outcomes of OC. In order to investigate the functional role of NBAT-1, pcDNA-NBAT-1 and empty vector were transfected into TOV112D and OVCAR-3 cell lines. Overexpressed NBAT-1 significantly inhibited cell proliferation, invasion, and migration in both TOV112D and OVCAR-3 cell lines. Finally, Western blot assay indicated that NBAT-1 may exert its function by targeting the ERK1/2 and AKT signaling pathways. In addition, tumor formation growth assay showed that overexpressed NBAT-1 significantly suppresses tumor growth in vivo. In conclusion, our study suggests that NBAT-1 acts as an anti-oncogene in the development of OC.
长链非编码RNA（lncRNA）已被证明参与卵巢癌（OC）的许多生物学过程。然而，其机制仍不清楚。在本研究中，我们在来自基因表达综合数据库（Gene Expression Omnibus）的两个样本量相对较大的独立数据集（GSE18520和GSE38666）中筛选出显著下调的NBAT-1，NBAT-1已被证明在乳腺癌、透明细胞肾细胞癌和神经母细胞瘤中发挥重要作用，但在OC中并非如此。我们发现，与无OC的正常卵巢组织相比，lncRNA NBAT-1在OC组织中明显下调（<0.001），且检测到的NBAT-1水平与国际妇产科联盟分期和肿瘤大小指南相关。此外，研究表明，较低水平的NBAT-1预示着OC的不良预后。为了研究NBAT-1的功能作用，将pcDNA-NBAT-1和空载体转染到TOV112D和OVCAR-3细胞系中。过表达的NBAT-1在TOV112D和OVCAR-3细胞系中均显著抑制细胞增殖、侵袭和迁移。最后，蛋白质免疫印迹分析表明，NBAT-1可能通过靶向ERK1/2和AKT信号通路发挥其功能。此外，肿瘤形成生长试验表明，过表达的NBAT-1在体内显著抑制肿瘤生长。总之，我们的研究表明，NBAT-1在OC的发生发展中起抑癌基因的作用。
