Wu Qihui, Ren Xiaolei, Zhang Yimin, Fu Xiaodan, Li Yimin, Peng Yulong, Xiao Qing, Li Tong, Ouyang Chunli, Hu Yixi, Zhang Yu, Zhou Wenjuan, Yan Wenguang, Guo Ke, Li Wei, Hu Yongbin, Yang Xiaojing, Shu Guang, Xue Haofan, Wei Zhangming, Luo Yonghong, Yin Gang
Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410008, China; Department of Pathology, School of Basic Medical Sciences, Central South University, Changsha, 410013, China.
Department of Pathology, School of Basic Medical Sciences, Central South University, Changsha, 410013, China.
Biochem Biophys Res Commun. 2018 Mar 18;497(4):1162-1170. doi: 10.1016/j.bbrc.2017.01.002. Epub 2017 Jan 3.
Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer. Although molecular diagnostic tools and targeted therapies have been developed over the past few decades, the survival rate is still rather low. Numerous researches suggest that some microRNAs (miRNAs) are key regulators of tumor progression. Among those miRNAs that has attracted much attention for their multiple roles in human cancers, the function of miR-221-3p in EOC has not been elucidated. Herein, we examined the expression of miR-221-3p in EOC patients and cell lines. Our data revealed that higher expression of miR-221-3p was linked to better overall survival in EOC patients. In-vitro experiments indicated that miR-221-3p inhibited EOC cell proliferation and migration. By performing subsequent systematic molecular biological and bioinformatic analyses, we found ADP-ribosylation factor (ARF) 4 is one of the putative target genes, the direct binding relationship was further confirmed by dual-luciferase reporter assay. Finally, a distinct gene expression between miR-221-3p and ARF4 in EOC group and normal group was identified, and the negative correlation between their expression levels in EOC specimens was further confirmed. Taken together, our research uncovered the tumor suppressive role of miR-221-3p in EOC and directly targeted ARF4, suggesting that miR-221-3p might be a novel potential candidate for clinical prognosis and therapeutics of EOC.
上皮性卵巢癌（EOC）是最致命的妇科癌症。尽管在过去几十年中已经开发了分子诊断工具和靶向治疗方法，但其生存率仍然相当低。大量研究表明，一些微小RNA（miRNA）是肿瘤进展的关键调节因子。在那些因其在人类癌症中的多种作用而备受关注的miRNA中，miR-221-3p在EOC中的功能尚未阐明。在此，我们检测了EOC患者和细胞系中miR-221-3p的表达。我们的数据显示，miR-221-3p的高表达与EOC患者更好的总生存期相关。体外实验表明，miR-221-3p抑制EOC细胞的增殖和迁移。通过随后进行的系统分子生物学和生物信息学分析，我们发现ADP-核糖基化因子（ARF）4是一个推定的靶基因，双荧光素酶报告基因实验进一步证实了它们之间的直接结合关系。最后，我们确定了EOC组和正常组中miR-221-3p和ARF4之间不同的基因表达，并进一步证实了它们在EOC标本中的表达水平呈负相关。综上所述，我们的研究揭示了miR-221-3p在EOC中的肿瘤抑制作用，并直接靶向ARF4，表明miR-221-3p可能是EOC临床预后和治疗的一个新的潜在候选者。
