Yang Aijun, Wang Xuenan, Yu Chunna, Jin Zhenzhen, Wei Lingxia, Cao Jinghe, Wang Qin, Zhang Min, Zhang Lin, Zhang Lei, Hao Cuifang
Center for Reproductive Medicine, Affiliated Hospital of Jining Medical University, Jining, Shandong 272029, P.R. China.
Department of Clinical Medicine, Jining Medical University, Jining, Shandong 272067, P.R. China.
Oncol Lett. 2017 Sep;14(3):3177-3184. doi: 10.3892/ol.2017.6501. Epub 2017 Jun 30.
Ovarian cancer is one of the most common types of gynecological malignancy worldwide, and is the fourth leading cause of cancer-associated mortality among women. Despite improvements in therapeutic treatments, the prognosis for epithelial ovarian cancer (EOC) remains poor, mainly due to the rapid growth and metastasis of ovarian cancer tumors. An increasing number of studies have indicated that microRNAs (miRNAs) are involved in the carcinogenesis and progression of human cancer, suggesting that miRNAs may be used in clinical prognosis and as a therapeutic target in EOC. The aim of the present study was to investigate the expression levels of miRNA-494 in EOC tissues and cell lines. The clinical significance of miRNA-494 in patients with EOC was also evaluated. The results demonstrated that miRNA-494 was significantly downregulated in EOC tissues and cell lines. Low expression levels of miRNA-494 were associated with poor prognostic features, including International Federation of Gynecology and Obstetrics stage, tumor size and lymph node metastasis. functional studies demonstrated that overexpression of miRNA-494 inhibited proliferation, migration and invasion in EOC cells. By contrast, knockdown of miRNA-494 enhanced cell growth, migration and invasion in EOC cells. Notably, sirtuin 1 (SIRT1) was identified as a direct target of miRNA-494 in EOC. Furthermore, MTT, cell migration and invasion assays verified that EOC cell proliferation, migration and invasion were completely restored with forced miRNA-494 expression and SIRT1 restoration. Together, these findings suggest that miRNA-494 is a potential prognostic marker, and may provide novel therapeutic regimens of targeted therapy for EOC.
卵巢癌是全球最常见的妇科恶性肿瘤类型之一,也是女性癌症相关死亡的第四大主要原因。尽管治疗方法有所改进,但上皮性卵巢癌(EOC)的预后仍然很差,主要是由于卵巢癌肿瘤的快速生长和转移。越来越多的研究表明,微小RNA(miRNA)参与人类癌症的发生和发展,这表明miRNA可用于临床预后评估,并作为EOC的治疗靶点。本研究的目的是调查miRNA-494在EOC组织和细胞系中的表达水平。还评估了miRNA-494在EOC患者中的临床意义。结果表明,miRNA-494在EOC组织和细胞系中显著下调。miRNA-494的低表达水平与不良预后特征相关,包括国际妇产科联盟分期、肿瘤大小和淋巴结转移。功能研究表明,miRNA-494的过表达抑制了EOC细胞的增殖、迁移和侵袭。相反,敲低miRNA-494可增强EOC细胞的生长、迁移和侵袭。值得注意的是,沉默调节蛋白1(SIRT1)被确定为EOC中miRNA-494的直接靶点。此外,MTT、细胞迁移和侵袭试验证实,通过强制表达miRNA-494和恢复SIRT1,EOC细胞的增殖、迁移和侵袭完全恢复。总之,这些发现表明miRNA-494是一种潜在的预后标志物,并可能为EOC提供新的靶向治疗方案。