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.

Key points: Upregulation of miR-183-5p: The study demonstrates significant upregulation of miR-183-5p in bladder carcinoma tissues and urine, especially in high-grade and metastatic cases, suggesting its potential as a non-invasive biomarker for BC diagnosis.Upregulation of miR-183-5p: The study demonstrates significant upregulation of miR-183-5p in bladder carcinoma tissues and urine, especially in high-grade and metastatic cases, suggesting its potential as a non-invasive biomarker for BC diagnosis. Urine-based Detection: miR-183-5p was effectively detected in urine samples, showing potential for early detection of BC through a non-invasive method, improving upon current diagnostic tools like cytology and cystoscopy. Tumor Suppressor Role of TPM1: The study confirms that TPM1 is significantly downregulated in BC, particularly in high-grade, muscle-invasive, and metastatic bladder cancers. Inverse Relationship: There is an inverse correlation between miR-183-5p expression and TPM1 levels, with miR-183-5p directly targeting TPM1 and suppressing its expression, contributing to cancer progression. Theranostic Role of miR-183-5p: This study positions miR-183-5p not just as a diagnostic marker but also as a potential therapeutic target (theranostic) that can be manipulated to inhibit bladder cancer progression. miR-183-5p and Disease Severity: The expression of miR-183-5p correlates with tumor grade, stage, and metastasis, making it a reliable marker for prognostication. High miR-183-5p levels are associated with worse clinical outcomes.