MicroRNA Expression Profile in Penile Cancer Revealed by Next-Generation Small RNA Sequencing

Abstract

Penile cancer (PeCa) is a relatively rare tumor entity but possesses higher morbidity and mortality rates especially in developing countries. To date, the concrete pathogenic signaling pathways and core machineries involved in tumorigenesis and progression of PeCa remain to be elucidated. Several studies suggested miRNAs, which modulate gene expression at posttranscriptional level, were frequently mis-regulated and aberrantly expressed in human cancers. However, the miRNA profile in human PeCa has not been reported before. In this present study, the miRNA profile was obtained from 10 fresh penile cancerous tissues and matched adjacent non-cancerous tissues via next-generation sequencing. As a result, a total of 751 and 806 annotated miRNAs were identified in normal and cancerous penile tissues, respectively. Among which, 56 miRNAs with significantly different expression levels between paired tissues were identified. Subsequently, several annotated miRNAs were selected randomly and validated using quantitative real-time PCR. Compared with the previous publications regarding to the altered miRNAs expression in various cancers and especially genitourinary (prostate, bladder, kidney, testis) cancers, the most majority of deregulated miRNAs showed the similar expression pattern in penile cancer. Moreover, the bioinformatics analyses suggested that the putative target genes of differentially expressed miRNAs between cancerous and matched normal penile tissues were tightly associated with cell junction, proliferation, growth as well as genomic instability and so on, by modulating Wnt, MAPK, p53, PI3K-Akt, Notch and TGF-β signaling pathways, which were all well-established to participate in cancer initiation and progression. Our work presents a global view of the differentially expressed miRNAs and potentially regulatory networks of their target genes for clarifying the pathogenic transformation of normal penis to PeCa, which research resource also provides new insights into future investigations aimed to explore the in-depth mechanisms of miRNAs and other small RNAs including piRNAs in penile carcinogenesis regulation and effective target-specific theragnosis.

TGF-β and microRNA Interplay in Genitourinary Cancers

“…The first NGS analysis of small RNAs expressed in penile cancers was published in 2015. Interestingly, the TGF-β signaling pathway was among the top enriched pathways predicted to be targeted by miRNAs differently expressed in penile cancer tissues compared with matched adjacent non-cancerous tissues [290]. Furthermore, TGFB3 and TGFBR2 were found within the top pathways involving miRNA-targeted genes disrupted in penile cancer [291].…”

MIR-107, MIR-223-3P and MIR-21-5P Reveals Potential Biomarkers in Penile Cancer

“…In addition, they reveal new signaling pathways and therapeutic molecular targets, correlated with carcinogenesis (Weidan et al, 2017). In PC, the first large-scale study with microRNAs analysis was conducted by Zhang et al, (2015), and some differentially expressed microRNAs were identified, such as miR-107, and miR-223-3p. These micro RNAs were described related with metastasis, invasion, transport, and colonization in cancer (Gao et al, 2016;Hu et al, 2016;Markou et al, 2016;Mavrakis et al, 2011).…”

Role of microRNA-4458 in patients with non-small-cell lung cancer

“…Approximately one half of microRNA (miR) genes are distributed at unstable sites of the genome, including fragile sites of chromatin and cleavage sites (2,3). There is a significant difference in the expression level of miRs in cancerous tissue and normal tissue (4). Based on their diversity and wide distribution throughout the genome, miRs may serve as an important tumor diagnostic method (5).…”