Expression of urinary miRNAs targeting NLRs inflammasomes in bladder cancer

Aim of the study: Inflammasome, a large complex of NOD-like receptors (NLRs), drives tumor growth and progression. The present study aimed at exploring the alteration in expression of urinary inflammasome-related microRNAs (miRNAs) in bladder cancer (BC). Our previous report demonstrated the up-regulation of NLRs genes (NLRP3, NLRP4, NLRP9 and NAIP) in urine sediments of patients harboring BC. The expression levels of miRNAs targeting these NLRs (miR-146a-5p, miR-106a-5p, miR-17-5p, miR-223-3p, miR-141-3p, miR-19a-3p, miR-145-5p, miR-185-5p) were assayed in the same patient cohort. Materials and methods: Forty-six subjects affected by BC, 28 healthy controls (CTR0) and 31 subjects with histologically confirmed bladder inflammation (CTR1) were recruited. Total RNA was extracted from urine sediment and resulting cDNA was used for amplification by real-time polymerase chain reaction. MiRNA expression levels were evaluated and compared among selected groups. Patients were further stratified according to tumor stage, grade and risk of recurrence and progression. Moreover, non-muscle invasive low-grade and high-grade (HG) BC patients were compared. Results: MiR 141-3p and miR-19a-3p expression decreased in CTR1 with respect to both BC and CTR0. In contrast, miR-146a-5p was up-regulated in BC compared with CTR0. MiR106a-5p, miR17-5p and miR19a-5p were significantly up-regulated in HG, high-risk (HR) and non-muscle invasive HG BC patients, while miR-185-5p was significantly higher in muscle invasive tumors, according to T stage stratification. Conclusion: The increased expression of miRNAs targeting NLRs in HG and HR BC patients is in accordance with the decrease in NLR mRNAs observed in our previous report. These data corroborate the direct role of NLR genes and respective regulatory miRNAs in BC making these inflammasome-related molecules a reliable non-invasive tool for BC diagnosis.