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

PLoS One. 2015 Jul 9;10(7):e0131336. doi: 10.1371/journal.pone.0131336. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Chromosome Mapping
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Male
  • MicroRNAs / chemistry
  • MicroRNAs / genetics*
  • Molecular Sequence Data
  • Penile Neoplasms / genetics*
  • Penile Neoplasms / surgery
  • RNA Folding
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / genetics
  • RNA, Small Untranslated / chemistry
  • RNA, Small Untranslated / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics

Substances

  • MicroRNAs
  • RNA, Small Interfering
  • RNA, Small Untranslated

Grants and funding

This work was supported by the National Natural Science Foundation of China (No.81401518, No. 31430028, http://www.nsfc.gov.cn/) (LZ); the National Natural Science Foundation of China (No. 81170698, No. 81370856, http://www.nsfc.gov.cn/) (CZL); the National Natural Science Foundation of China (No. 31370983, http://www.nsfc.gov.cn/) (DHZ); Anhui Provincial Natural Science Foundation (No.1408085QH180, http://www.ahkjt.gov.cn/) (LZ), the Clinical Key Subjects Program of the Ministry of Public Health of China (Urology, http://www.nhfpc.gov.cn/) (CZL), the cultivation project for NSFC at Anhui Medical University (No. 2013KJ14, http://www.ayfy.com) (LZ) and the Key Project of the Chinese Ministry of Education (No. 212080, http://www.moe.edu.cn/) (DHZ). The funders had no roles in study design, data collection and analysis, decision to publish or preparation of the manuscript.