Author:
Hu Yang,Xie Hong,Liu Yankun,Liu Weiying,Liu Min,Tang Hua
Abstract
Abstract
Background
MicroRNAs (miRNAs) play important roles in cancer initiation and development. Epithelial–mesenchymal transition (EMT) is a form of cellular plasticity that is critical for embryonic development and metastasis. The purpose of the study was to determine the function and mechanism of miR-484 in initiation and development of cervical cancer (CC).
Methods
We determined the expression levels of miR-484 in cervical cancer tissues and cell lines with RT-qPCR. Prediction algorithms and EGFP reporter assay were performed to evaluate the targets for miR-484. MTT assay, colony formation assay, flow cytometric analysis, transwell cell migration and invasion assays, and detection of EMT markers were employed to investigate the roles of miR-484 and the targets in regulation of cell proliferation and EMT process. We also used rescue experiments to confirm the effect of miR-484 on CC cells through directly regulating the expression of its targets.
Results
Firstly we found miR-484 was down-regulated in cervical cancer tissues and cell lines compared with their matched non-cancerous tissues or normal cervical keratinocytes cells. Further studies revealed that overexpression of miR-484 suppressed the cell proliferation, while exacerbates apoptosis. Besides, miR-484 suppressed cellular migration, invasion and EMT process of CC cells. EGFP reporter assay showed that miR-484 binds to ZEB1 and SMAD2 3′UTR region and reduced their expression. The expression of miR-484 had reverse correlation with SMAD2/ZEB1, and SMAD2/ZEB1 had positive correlation with each other in cervical cancer tissues and cell lines. Furthermore, the ectopic expression of ZEB1 or SMAD2 could rescue the malignancies suppressed by miR-484, suggesting that miR-484 down-regulates ZEB1 and SMAD2 to repress tumorigenic activities.
Conclusion
We found miR-484 inhibits cell proliferation and the EMT process by targeting both ZEB1 and SMAD2 genes and functions as a tumor suppressor, which may served as potential biomarkers for cervical cancer.
Funder
Natural Science Foundation of Tianjin
National Natural Science Foundation of China
Natural Science Foundation of Tianjin City
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
Reference44 articles.
1. Tjalma WA. Diagnostic performance of dual-staining cytology for cervical cancer screening: a systematic literature review. Eur J Obstet Gynecol Reprod Biol. 2017;210:275–80.
2. Banister CE, Liu C, Pirisi L, Creek KE, Buckhaults PJ. Identification and characterization of HPV-independent cervical cancers. Oncotarget. 2017. doi:10.18632/oncotarget.14533.
3. Tjalma WA, Kim E, Vandeweyer K. The impact on women’s health and the cervical cancer screening budget of primary HPV screening with dual-stain cytology triage in Belgium. Eur J Obstet Gynecol Reprod Biol. 2017;S0301–2115(17):30010–6.
4. Liu C, Wang J, Hu Y, Xie H, Liu M, Tang H. Upregulation of kazrin F by miR-186 suppresses apoptosis but promotes epithelial–mesenchymal transition to contribute to malignancy in human cervical cancer cells. Chin J Cancer Res. 2017. doi:10.21147/j.issn.1000-9604.2017.01.00.
5. Kim VN, Han J, Siomi MC. Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol. 2009;10:126–39.
Cited by
63 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献