New England Section of the American Urological Association

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MiR-141-3b Expression in Urothelial Carcinoma of the Bladder and Upper Tract
Kelly Crane, MD, Kailey Hooper, BS, Travis Sullivan, MS, Kimberly M. Rieger-Christ, Ph.D.
Lahey Clinic, Burlington, MA, USA.

BACKGROUND: MicroRNAs (miRNA/miR) are involved in regulation of gene expression. We worked to identify miRNA involved in the transition between noninvasive and invasive urothelial carcinoma of the bladder and upper tract and evaluate conflicting data in current literature. In our previous study of upper tract urothelial carcinoma (UTUC) biopsy specimens collected from three institutions, we analyzed miRNA expression in a cohort of 83 patients, and we identified a panel of miRNA associated with the invasive phenotype. One of these, miR-141, was significantly downregulated in invasive biopsy and nephroureterectomy specimens. Research on miR-141 in bladder cancer is limited, and existing findings are inconsistent.
METHODS: In an effort to identify a potential role of miR-141 in UTUC and bladder cancer, we performed cell culture-based assays to evaluate the effects of altered expression levels of miR-141 on bladder cancer phenotypes. Pre-miR-141 constructs were transfected into two urothelial bladder cancer cell lines (TCCSUP and EJ) to evaluate any possible change in proliferation, migration, and invasive potential: phenotypes associated with epithelial to mesenchymal transition.
RESULTS:Transfection (forced expression) of pre-miR 141 was verified via qRT-PCR in both cell lines. Increased levels of miR-141 in TCCSUP resulted in a decreased rate of proliferation, migration, and invasion with t-test of p=0.024 at 48hr, 0.015, and 0.028 respectively. Transfection of pre-miR-141 into EJ resulted in a decreased rate of proliferation, migration, and invasion with t-test of p=0.049 at 48hr, 0.003, and 0.0004 respectively.
CONCLUSIONS:
Transfection of miR-141 into bladder cancer cells resulted in decreased rates of cell proliferation, migration, and invasion. Our data supports a role of miR-141 as a tumor suppressor microRNA in bladder cancer and UTUC. This data could help lead to a clinical biomarker and therapeutic target in urothelial carcinoma.
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