Role of microRNA-183 based theranostics through targeting TPM1 in bladder cancer

Abstract

BACKGROUND: MicroRNA-183 (miR-183-5p), a noncoding RNA, is upregulated in bladder carcinoma (BC). Although it has been implicated in oncogenesis, its precise regulatory effects and biological functions remain unclear. Tropomyosin-1 (TPM1) was shown to be downregulated in solid tumors and was previously identified as a novel tumor suppressor gene. OBJECTIVES: Our study focuses on the prognostic, diagnostic, and therapeutic potential of miR-183-5p in bladder carcinoma and assess TPM1 gene targets and their modulatory functions. METHODS: Urine cytology, cystectomy and transurethral resection (TUR) biopsies from 148 BC patients were collected. TPM1 protein and miR-183-5p expressions were assessed through immunohistochemistry (IHC) and real-time PCR respectively. In vitro assay investigated the effect of miR-183-5p on TPM1mRNA in bladder carcinoma cell lines, then confirmed by comparing miR-183-5p mimics in non-cancerous and urothelial carcinoma cell lines. Concomitant TPM1 gene expression was examined, and the theranostic miR-183-5p potential was evaluated. RESULTS: Upregulation of miR-183-5p expression in BC tissue biopsies and urine cytologies was noted, contrasting the downregulation of TPM1 protein expression in the high-grade, high-stage, lymph node metastatic BC tissues (in comparison to non-cancerous, low-grade, low-stage non-lymph node metastasizing BCs). Moreover, the miR-183-5p oncogenic influence was responsive in targeting TPM1 gene at 3'UTR region, and miR‑183‑5p.1 restricted TPM1 expression in T24 cells. CONCLUSION: This study provides the first illustration of the miR-183-5p-TPM1 axis in bladder carcinoma, supporting the theranostic role of miR-183-5p as an onco-miR in BC progression, diagnosis, and prognostication.