The authors declare that they have no competing interests.
XZ conceived the project; JL designed the experiments and carried out the majority of the experiments; JC helped to culture cells; all authors discussed the results; JL and XZ wrote the manuscript. All authors read and approved the final manuscript.
Distant metastasis is the major cause of cancer-related death, and epithelial-to-mesenchymal transition (EMT) has a critical role in this process. Accumulating evidence indicates that EMT can be regulated by microRNAs (miRNAs). miR-221, as oncogenes in several human cancers, was significantly up-regulated in bladder cancers. However, the role of miR-221 in the progression of bladder cancer metastasis remains largely unknown.
We used qRT-PCR and western blot to accurately measure the levels of miR-221, STMN1 and EMT markers in TGFβ1 induced EMT of bladder cancer cells. miR-221 inhibitors were re-introduced into bladder cancer cells to investigate its role on tumor metastasis which was measured by MTT, wound healing, transwell invasion and adherent assays. Luciferase reporter assay was used to reveal the target gene of miR-221.
miR-221 expression was greatly increased by TGFβ1 in bladder cancer cell. miR-221 inhibition reversed TGFβ1 induced EMT by sharply increasing the expression of the epithelial marker E-cadherin and decreasing the expression of the mesenchymal markers vimentin, Fibroactin and N-cadherin. Furthermore, miR-221 expression is positively correlated with malignant potential of bladder cancer cell through promoting loss of cell adhesion and prometastatic behavior. Luciferase reporter assay revealed that miR-221 negatively regulates STMN1 expression by direct targeting to the 3′UTR region of STMN1.
Our study demonstrated that miR-221 facilitated TGFβ1-induced EMT in human bladder cancer cells by targeting STMN1 and represented a promising therapeutic target in the process of metastasis.
He XX, Guo AY, Xu CR, Chang Y, Xiang GY, Gong J, et al. Bioinformatics analysis identifies miR-221 as a core regulator in hepatocellular carcinoma and its silencing suppresses tumor properties. Oncol Rep. 2014;32(3):1200–10. PubMed
Stinson S, Lackner MR, Adai AT, Yu N, Kim HJ, O’Brien C, et al. miR-221/222 targeting of trichorhinophalangeal 1 (TRPS1) promotes epithelial-to-mesenchymal transition in breast cancer. Sci Signal. 2011;4(186):t5. CrossRef
- miR-221 facilitates the TGFbeta1-induced epithelial-mesenchymal transition in human bladder cancer cells by targeting STMN1
- BioMed Central
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