Background: MicroRNAs (miRNAs) are small non-coding RNAs that silence their cognate target genes by specifically binding and cleaving messenger RNAs or inhibiting their translation. In this study, we explored whether miRNA-141 and miRNA-200b are involved in regulation of the invasive ability and epithelial-mesenchymal transition (EMT) of bladder cancer cells in vitro. We also evaluated their potential as biomarkers for deciding the extent of pelvic lymph node dissection (PLND) required during radical cystectomy.
Methods: Pri- and anti-miR cell lines were constructed. The invasive capacity of the cells was tested using a cell invasion assay. The MMP-2, MMP-9 and EMT-related markers were validated through Western blotting analysis. Seventy-eight urine samples from patients undergoing cystectomy and super-extended lymph node dissection were evaluated by qRT-PCR.
Results: Loss of expression of miRNA-141 and miRNA-200b was associated with increased invasion and migration ability, upregulated MMP-2, MMP-9, vimentin and N-cadherin expression, and downregulated E-cadherin expression in bladder cancer cell lines. Urine miRNA-141 and miRNA-200b levels could discriminate patients with lymph node metastasis from those who were lymph node negative (AUC: 0.704 and 0.674, respectively).
Conclusion: MiRNA-141 and miRNA-200b play important roles in the invasive ability and EMT phenotype of bladder cancer. Detection of miRNA-141 and miRNA-200b can help to identify patients undergoing cystectomy who are likely to have lymph node metastasis, and therefore those who may benefit from super-extended PLND.