Downregulation of miR-145 is associated with perineural invasion in penile carcinoma

Abstract

Background: Human papillomavirus (HPV) infection is a risk factor for penile cancer (PC). The miR-145 expression has been correlated to this virus genomic amplification. In this context, this work aims to determine the expression level of miR-145 in penile tumors infected by high-risk HPV and correlate it with the clinicopathological characteristics of the tumor and protein expression of p53.Methods: Formalin-fixed paraffin-embedded from 52 patients with PC, at diagnosis and prior to any cancer treatment, were obtained. HPV identification was performed by nested type PCR, and miR-145 expression was obtained by qRT-PCR. Immunohistochemical analysis of p53 and Ki-67 was performed.Results: Tumoral miR-145 expression was significantly lower compared to adjacent tissue. Additionally, there was a significant reduction of miR-145 expression in invasion perineural, histological associated HPV, and absence of p53 expression in positive HPV cases. HPV infection was detected in 86.5%, the most frequent HPV16. Reduced disease-free survival was observed in patients with low expression of miR-145.Conclusions: Our data suggest that the underexpression of miR-145 may be triggered by HPV action, decreasing protein expression of p53, and being correlated with perineural invasion. Therefore, the deregulation of miR-145 provides clues as to the potential role in penile carcinogenesis and is also a potential candidate for validation in noninvasive samples.

Disruption of miRNA-mRNA Networks Defines Novel Molecular Signatures for Penile Carcinogenesis

“…To our knowledge, to date, only 11 studies have investigated the differential expression of microRNAs (miRNAs) in this disease [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. miRNAs are a class of small non-coding RNAs (ncRNAs) that regulate gene expression post-transcriptionally by repressing translation and/or initiating mRNA degradation [ 21 ].…”

Non-Coding RNA in Penile Cancer

“…In another study, our group also observed that miR-145-5p is a potential biomarker for perineural invasion ( 13 ), an indicator of worse survival in patients with penile cancer ( 55 ). MiR-145-5p also has therapeutic potential since the use of mimics of this microRNA in cervical cancer can inhibit cell proliferation ( 56 ) and metastasis in ovarian cancer ( 57 ).…”

“…Thus, biological markers that can predict or assist in diagnosing this phenomenon are of great clinical importance. Some markers based on ncRNAs have been investigated, especially those associated with lymph node metastasis ( 11 , 12 ), perineural invasion ( 13 ), and HPV ( 14 ).…”