Bai Ru, Dou Kaikai, Wu Yang, Ma Yongjing, Sun Jianmin
School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China.
School of Pharmacy, Ningxia Medical University, Yinchuan, China.
J Cancer. 2020 Mar 13;11(12):3433-3445. doi: 10.7150/jca.40604. eCollection 2020.
miRNAs are involved in the tumorigenesis of various malignancies. In the current study, we found that miR-194-5p expression is downregulated in ovarian cancer tissues, and downregulation of miR-194-5p expression promotes proliferation, invasion and migration of human ovarian cancer cells and ovarian tumor growth in nude mice. We further found that IGF1R and PPFIBP are targets of miR-194-5p, and downregulation of miR-194-5p expression increases IGF1R and PPFIBP expression, resulting in increased proliferation, invasion and migration of ovarian cancer cells. Moreover, we showed that NF-κB can bind to the promoter region of miR-194-5p, and negatively regulate the expression of miR-194-5p in ovarian cancer cells. Taken together, our results suggested a NF-κB modulated miR-194-5p/IGF1R/ PPFIBP axis that is crucial for the tumorigenesis of ovarian cancer, which provides a new insight into the development of ovarian cancer.
微小RNA（miRNAs）参与多种恶性肿瘤的发生发展。在本研究中，我们发现miR-194-5p在卵巢癌组织中表达下调，miR-194-5p表达下调促进人卵巢癌细胞的增殖、侵袭和迁移以及裸鼠卵巢肿瘤生长。我们进一步发现胰岛素样生长因子1受体（IGF1R）和蛋白酪氨酸磷酸酶家族成员PPFIBP是miR-194-5p的靶标，miR-194-5p表达下调会增加IGF1R和PPFIBP的表达，导致卵巢癌细胞增殖、侵袭和迁移增加。此外，我们表明核因子κB（NF-κB）可与miR-194-5p的启动子区域结合，并负向调节卵巢癌细胞中miR-194-5p的表达。综上所述，我们的结果提示了一种NF-κB调控的miR-194-5p/IGF1R/PPFIBP轴，该轴对卵巢癌的发生发展至关重要，为卵巢癌的研究提供了新的见解。
