Diagnostic and Prognostic Potential of MicroRNA Maturation Regulators Drosha, AGO1 and AGO2 in Urothelial Carcinomas of the Bladder

Abstract

Bladder cancer still requires improvements in diagnosis and prognosis, because many of the cases will recur and/or metastasize with bad outcomes. Despite ongoing research on bladder biomarkers, the clinicopathological impact and diagnostic function of miRNA maturation regulators Drosha and Argonaute proteins AGO1 and AGO2 in urothelial bladder carcinoma remain unclear. Therefore, we conducted immunohistochemical investigations of a tissue microarray composed of 112 urothelial bladder carcinomas from therapy-naïve patients who underwent radical cystectomy or transurethral resection and compared the staining signal with adjacent normal bladder tissue. The correlations of protein expression of Drosha, AGO1 and AGO2 with sex, age, tumor stage, histological grading and overall survival were evaluated in order to identify their diagnostic and prognostic potential in urothelial cancer. Our results show an upregulation of AGO1, AGO2 and Drosha in non-muscle-invasive bladder carcinomas, while there was increased protein expression of only AGO2 in muscle-invasive bladder carcinomas. Moreover, we were able to differentiate between non-muscle-invasive and muscle-invasive bladder carcinoma according to AGO1 and Drosha expression. Finally, despite Drosha being a discriminating factor that can predict the probability of overall survival in the Kaplan–Meier analysis, AGO1 turned out to be independent of all clinicopathological parameters according to Cox regression. In conclusion, we assumed that the miRNA processing factors have clinical relevance as potential diagnostic and prognostic tools for bladder cancer.

POU2F2 promotes the proliferation and motility of lung cancer cells by activating AGO1

“…We then investigated the mechanisms underlying POU2F2 promoting the prolifetion, and motility of lung cancer cells in vitro. The effects of AGO1 in the progression of lung cancer has been widely revealed [ 20 , 21 ]. Through the prediction by Jasper website ( http://jaspar.genereg.net ), we found POU2F2 could target AGO1 promoter regions, including three different sites (Fig.…”

MicroRNA-153-5p promotes the proliferation and metastasis of renal cell carcinoma via direct targeting of AGO1

“…AGO1 was found to suppress tumor angiogenesis and predict a better prognosis via translational inhibition of vascular endothelial growth factor (VEGF) 35 . It has been reported AGO1 acted as a biomarker for colon cancer, melanoma, and muscle-invasive bladder carcinomas [36][37][38] . However, the role of AGO1 in ccRCC is still unknown.…”

Argonaute Proteins Take Center Stage in Cancers

“…Furthermore, AGO2 upregulation was implicated as an adverse prognostic biomarker for urothelial carcinoma of the bladder [ 98 , 99 ]. Based on the analysis of 106 cases, high expression of AGO2 correlated both with metastasis and lower overall survival of the patients ( Figure 3 c) [ 98 ].…”

“…Based on the analysis of 106 cases, high expression of AGO2 correlated both with metastasis and lower overall survival of the patients ( Figure 3 c) [ 98 ]. Looking in detail, the assessment of AGO2 expression levels in bladder tissues derived from urothelial carcinoma was sufficient to discriminate between muscle invasive and non-muscle invasive tumors [ 99 ]. Moreover, the assessment of AGO2 expression may serve as a prognostic factor for grading patients suffering from colorectal cancer [ 100 ].…”

“… ( a – k ) Dysregulation of AGO1–4 in cancers, based on refs [ 7 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 ]. Created with BioRender.com (accessed date: 21 January 2021).…”