Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
Gynecol Oncol. 2010 Dec;119(3):543-8. doi: 10.1016/j.ygyno.2010.08.034. Epub 2010 Sep 24.
Aberrant expression of microRNAs (miRNAs) has been implicated in ovarian carcinoma. However, roles of miRNAs in ovarian caner metastasis have not been comprehensively addressed. This work is aimed to identify selected miRNAs involved in ovarian cancer metastasis.
We examined the distinct miRNA expression profiles between paired high-metastatic human serous ovarian cancer cell SKOV-3ip and low-metastatic human serous ovarian cell SKOV-3 using miRNA microarray. Subsequently, a validation with Real-time RT-PCR was performed for miR-22 expression level, and a functional study was carried out for miR-22.
Through a screen with microarray, we found there were a variety of miRNAs differentially expressed between paired high and low metastatic serous ovarian cancer cells. Particularly, miR-22 was identified as a potential metastasis-inhibitor in ovarian cancer. There was a negative correlation between miR-22 expression and the metastatic potential in ovarian cancer cells. Furthermore, both gain-of-function and loss-of-function studies displayed an inhibitory effect of miR-22 on cell migration and invasion in vitro without significantly affecting cell viability and apoptosis. Subsequent bioinformatics analysis revealed that miR-22 might regulate multiple pro-metastatic genes, which could provide an explanation to the inhibitory effects of miR-22 on cell migration and invasion.
Taken together, our findings suggested that miR-22 might be involved in inhibiting ovarian cancer metastasis.
微小 RNA（miRNA）的异常表达与卵巢癌有关。然而，miRNA 在卵巢癌转移中的作用尚未得到全面阐述。本研究旨在鉴定参与卵巢癌转移的选定 miRNA。
我们使用 miRNA 微阵列检查配对的高转移性人浆液性卵巢癌细胞 SKOV-3ip 和低转移性人浆液性卵巢细胞 SKOV-3 之间的独特 miRNA 表达谱。随后，通过实时 RT-PCR 对 miR-22 表达水平进行验证，并对 miR-22 进行功能研究。
通过微阵列筛选，我们发现配对的高转移性和低转移性浆液性卵巢癌细胞之间存在多种差异表达的 miRNA。特别是，miR-22 被鉴定为卵巢癌中潜在的转移抑制剂。miR-22 的表达与卵巢癌细胞的转移潜能呈负相关。此外，功能获得和功能丧失研究均显示 miR-22 对体外细胞迁移和侵袭具有抑制作用，而对细胞活力和凋亡无明显影响。随后的生物信息学分析表明，miR-22 可能调节多种促转移基因，这可以解释 miR-22 对细胞迁移和侵袭的抑制作用。
综上所述，我们的研究结果表明，miR-22 可能参与抑制卵巢癌转移。
