Expression of urinary miRNAs targeting NLRs inflammasomes in bladder cancer
Ettore Mearini1, Giulia Poli2, Giovanni Cochetti1
1Department of Surgical and Biomedical Sciences, Institute of Urological, Andrological Surgery and Minimally Invasive Techniques.
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.
Insights
Urinary microRNAs (miRNAs) targeting NOD-like receptors (NLRs) show altered expression in bladder cancer (BC). Specific miRNAs are elevated in high-grade and high-risk BC, suggesting their role in BC progression and potential as diagnostic biomarkers.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- The inflammasome complex, involving NOD-like receptors (NLRs), is implicated in tumor progression.
- Previous research indicated elevated NLR gene expression in urine sediments of bladder cancer (BC) patients.
- This study investigates urinary microRNA (miRNA) expression targeting these NLRs in BC.
Purpose of the Study:
- To explore alterations in urinary inflammasome-related miRNA expression in bladder cancer (BC).
- To assess the expression levels of specific miRNAs targeting NLRs in a cohort of BC patients and controls.
Main Methods:
- Recruitment of 46 BC patients, 28 healthy controls (CTR0), and 31 subjects with bladder inflammation (CTR1).
- Total RNA extraction from urine sediment, followed by cDNA synthesis and real-time polymerase chain reaction (PCR) for miRNA quantification.
- Comparison of miRNA expression levels among groups, with stratification by tumor stage, grade, and risk.
Main Results:
- MiR-141-3p and miR-19a-3p expression decreased in bladder inflammation controls (CTR1) compared to BC and healthy controls (CTR0).
- miR-146a-5p was upregulated in BC patients relative to CTR0.
- Elevated miR106a-5p, miR17-5p, and miR19a-5p were observed in high-grade (HG) and high-risk (HR) BC, while miR-185-5p was higher in muscle-invasive tumors.
Conclusions:
- Increased expression of NLR-targeting miRNAs in HG and HR BC aligns with previous findings of decreased NLR mRNAs.
- These inflammasome-related molecules demonstrate a direct role in BC.
- Urinary miRNAs represent a promising, non-invasive tool for BC diagnosis.
