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MicroRNA and transcription factor co-regulatory networks and subtype classification of seminoma and non-seminoma in testicular germ cell tumors
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MicroRNA and transcription factor co-regulatory networks and subtype classification of seminoma and non-seminoma in testicular germ cell tumors
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Journal Article
MicroRNA and transcription factor co-regulatory networks and subtype classification of seminoma and non-seminoma in testicular germ cell tumors
2020
Overview
Recent studies have revealed that feed-forward loops (FFLs) as regulatory motifs have synergistic roles in cellular systems and their disruption may cause diseases including cancer. FFLs may include two regulators such as transcription factors (TFs) and microRNAs (miRNAs). In this study, we extensively investigated TF and miRNA regulation pairs, their FFLs, and TF-miRNA mediated regulatory networks in two major types of testicular germ cell tumors (TGCT): seminoma (SE) and non-seminoma (NSE). Specifically, we identified differentially expressed mRNA genes and miRNAs in 103 tumors using the transcriptomic data from The Cancer Genome Atlas. Next, we determined significantly correlated TF-gene/miRNA and miRNA-gene/TF pairs with regulation direction. Subsequently, we determined 288 and 664 dysregulated TF-miRNA-gene FFLs in SE and NSE, respectively. By constructing dysregulated FFL networks, we found that many hub nodes (12 out of 30 for SE and 8 out of 32 for NSE) in the top ranked FFLs could predict subtype-classification (Random Forest classifier, average accuracy ≥90%). These hub molecules were validated by an independent dataset. Our network analysis pinpointed several SE-specific dysregulated miRNAs (miR-200c-3p, miR-25-3p, and miR-302a-3p) and genes (
EPHA2, JUN, KLF4, PLXDC2, RND3, SPI1
, and
TIMP3
) and NSE-specific dysregulated miRNAs (miR-367-3p, miR-519d-3p, and miR-96-5p) and genes (
NR2F1
and
NR2F2
). This study is the first systematic investigation of TF and miRNA regulation and their co-regulation in two major TGCT subtypes.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 631/553
/ Gene Expression Regulation, Neoplastic - genetics
/ Gene Regulatory Networks - genetics
/ Genes
/ Genomes
/ Humanities and Social Sciences
/ Humans
/ Male
/ miRNA
/ Neoplasms, Germ Cell and Embryonal - classification
/ Neoplasms, Germ Cell and Embryonal - genetics
/ Science
/ Seminoma
/ Testes
/ Testicular Neoplasms - classification
/ Testicular Neoplasms - genetics
/ Tissue inhibitor of metalloproteinase 3
/ Transcription Factors - genetics
/ Tumors
