Zhang Mingting, Xu Qingli, Yan Shufen, Li Zhigang, Yan Wei, Jia Xiaojing
Department of Gynecology and Obstetrics, Women and Infants Hospital of Zhengzhou, Zhengzhou, Henan 450012, P.R. China.
Department of Pharmacy, Women and Infants Hospital of Zhengzhou, Zhengzhou, Henan 450012, P.R. China.
Oncol Rep. 2016 May;35(5):3106-14. doi: 10.3892/or.2016.4651. Epub 2016 Mar 3.
MicroRNAs (miRNAs) play a pivotal role in cancer progression and development, representing novel therapeutic tools for cancer therapy. Forkhead box Q1 (FOXQ1) functions as an oncogene in various cancer types. However, the functional significance of FOXQ1 in cervical cancer remains unknown. In this study, we investigated the biological function of FOXQ1 in cervical cancer and tested whether or not FOXQ1 can be targeted and regulated by specific miRNAs. We found that FOXQ1 was highly expressed in cervical cancer cell lines. Knockdown of FOXQ1 by small interfering RNA (siRNA) significantly suppressed the proliferation and epithelial-mesenchymal transition (EMT) of cervical cancer cells. FOXQ1 was predicted as a target gene of microRNA-506 (miR-506), and this prediction was validated by dual-luciferase reporter assay. Quantitative real-time PCR and western blot analyses demonstrated that mRNA and protein expression was negatively regulated by miR-506. The expression of miR-506 was downregulated in cervical cancer tissues, and miR-506 expression was inversely correlated with FOXQ1 expression in cervical cancer. The overexpression of miR-506 dramatically suppressed the proliferation and EMT of cervical cancer cells that mimicked the suppression of FOXO1 siRNA. Furthermore, the restoration of FOXQ1 expression significantly reversed the inhibitory effect of miR-506. Overall, our study demonstrated that miR-506 inhibited the proliferation and EMT of cervical cancer cells by targeting FOXQ1 and provided evidence that the miR-506/FOXQ1 axis plays an important role in the pathogenesis of cervical cancer, representing potential molecular targets for the development of anticancer agents for cervical cancer treatment.
微小RNA（miRNA）在癌症进展和发展中起关键作用，是癌症治疗的新型治疗工具。叉头框Q1（FOXQ1）在多种癌症类型中作为癌基因发挥作用。然而，FOXQ1在宫颈癌中的功能意义尚不清楚。在本研究中，我们研究了FOXQ1在宫颈癌中的生物学功能，并测试了FOXQ1是否可以被特定的miRNA靶向和调控。我们发现FOXQ1在宫颈癌细胞系中高表达。通过小干扰RNA（siRNA）敲低FOXQ1可显著抑制宫颈癌细胞的增殖和上皮-间质转化（EMT）。FOXQ1被预测为微小RNA-506（miR-506）的靶基因，双荧光素酶报告基因检测验证了这一预测。定量实时PCR和蛋白质印迹分析表明，miR-506对mRNA和蛋白质表达具有负调控作用。miR-506在宫颈癌组织中的表达下调，且miR-506表达与宫颈癌中FOXQ1表达呈负相关。miR-506的过表达显著抑制了宫颈癌细胞的增殖和EMT，这与FOXO1 siRNA的抑制作用相似。此外，FOXQ1表达的恢复显著逆转了miR-506的抑制作用。总体而言，我们的研究表明，miR-506通过靶向FOXQ1抑制宫颈癌细胞的增殖和EMT，并提供证据表明miR-506/FOXQ1轴在宫颈癌发病机制中起重要作用，是开发宫颈癌治疗抗癌药物的潜在分子靶点。
