Paudel Dhruba, Zhou Wei, Ouyang Yiqin, Dong Shengnan, Huang Qingting, Giri Ranjana, Wang Jianjun, Tong Xiaowen
Department of Gynecology and Obstetrics, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Gynecology and Obstetrics, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
Gene. 2016 Jul 15;586(1):48-55. doi: 10.1016/j.gene.2016.04.001. Epub 2016 Apr 2.
To evaluate the clinical significance of microRNA (miR)-130b-Runt domain transcription factor (RUNX3) axis and its effects on oncogenic phenotypes of human epithelial ovarian cancer (EOC).
QRT-PCR was performed to detect the expression of miR-130b and RUNX3 mRNA in 100 EOC and 20 normal ovarian tissues. The associations between miR-130b and/or RUNX3 expression and various clinicopathological features of EOC patients were statistically analyzed. Then, the effects of miR-130b-RUNX3 axis on migration and invasion of EOC cells were assessed in vitro.
miR-130b expression was downregulated, while RUNX3 mRNA was upregulated, in EOC tissues compared to normal ovarian tissues (both P=0.001). Importantly, the expression level of miR-130b in EOC tissues was negatively correlated with that of RUNX3 mRNA significantly. Additionally, miR-130b-low and/or RUNX3-high expression were all closely correlated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage (all P<0.05). Moreover, overexpression of miR-130b reduced the expression of RUNX3 and inhibited cancer cell migration and invasion of EOC cells, whereas knockdown of miR-130b increased the expression of RUNX3 and promoted cancer cell migration and invasion of EOC cells. After that, the impaired motility of the miR-130b overexpression cells was recovered partly by the expression of RUNX3. Furthermore, the knockdown of RUNX3 also gave rise to a decrease in cell migration and invasion.
Our data reveal that the dysregulation of miR-130b-RUNX3 axis may play important roles in EOC development and progression, and the loss of miR-130b may contribute to the malignant biological behavior of EOC cells via regulating the expression of RUNX3, implying their potentials as promising markers for predicting EOC progression and as candidate targets for gene therapy.
评估微小RNA（miR）-130b- runt结构域转录因子（RUNX3）轴的临床意义及其对人上皮性卵巢癌（EOC）致癌表型的影响。
采用实时定量聚合酶链反应（QRT-PCR）检测100例EOC组织和20例正常卵巢组织中miR-130b和RUNX3 mRNA的表达。对miR-130b和/或RUNX3表达与EOC患者各种临床病理特征之间的相关性进行统计学分析。然后，在体外评估miR-130b-RUNX3轴对EOC细胞迁移和侵袭的影响。
与正常卵巢组织相比，EOC组织中miR-130b表达下调，而RUNX3 mRNA上调（均P=0.001）。重要的是，EOC组织中miR-130b的表达水平与RUNX3 mRNA的表达水平呈显著负相关。此外，miR-130b低表达和/或RUNX3高表达均与国际妇产科联盟（FIGO）晚期密切相关（均P<0.05）。此外，miR-130b的过表达降低了RUNX3的表达，并抑制了EOC细胞的癌细胞迁移和侵袭，而miR-130b的敲低增加了RUNX3的表达，并促进了EOC细胞的癌细胞迁移和侵袭。之后，RUNX3的表达部分恢复了miR-130b过表达细胞受损的运动能力。此外，RUNX3的敲低也导致细胞迁移和侵袭减少。
我们的数据表明，miR-130b-RUNX3轴的失调可能在EOC的发生和发展中起重要作用，miR-130b的缺失可能通过调节RUNX3的表达促进EOC细胞的恶性生物学行为，这意味着它们有望成为预测EOC进展的标志物和基因治疗的候选靶点。
