Title

MicroRNA and transcription factor co-regulatory networks and subtype classification of seminoma and non-seminoma in testicular germ cell tumors

Authors

Guimin Qin, The University of Texas Health Science Center at Houston
Saurav Mallik, The University of Texas Health Science Center at Houston
Ramkrishna Mitra, Thomas Jefferson UniversityFollow
Aimin Li, The University of Texas Health Science Center at Houston
Peilin Jia, The University of Texas Health Science Center at Houston
Christine M. Eischen, Thomas Jefferson UniversityFollow
Zhongming Zhao, The University of Texas Health Science Center at Houston

Document Type

Article

Publication Date

1-21-2020

Comments

This article is the author’s final published version in Scientific Reports, Volume 10, Issue 1, January 2020, Article number 852.

The published version is available at https://doi.org/10.1038/s41598-020-57834-w. Copyright © Qin et al.

Abstract

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.

Recommended Citation

Qin, Guimin; Mallik, Saurav; Mitra, Ramkrishna; Li, Aimin; Jia, Peilin; Eischen, Christine M.; and Zhao, Zhongming, "MicroRNA and transcription factor co-regulatory networks and subtype classification of seminoma and non-seminoma in testicular germ cell tumors" (2020). Department of Cancer Biology Faculty Papers. Paper 166.
https://jdc.jefferson.edu/cbfp/166

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

PubMed ID

31965022

Language

English