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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2018.00422

Identification of miR-200c and miR141-mediated lncRNA-mRNA crosstalks in muscle-invasive bladder cancer subtypes

  • 1Ural Federal University, Russia
  • 2Southern Medical University, China
  • 3Ural Branch of the Russian Academy of Sciences (RAS), Russia
  • 4Inner Mongolia University of Science and Technology, China

Basal and luminal subtypes of muscle-invasive bladder cancer (MIBC) have distinct molecular profiles and heterogeneous clinical behaviors. The interactions between mRNAs and lncRNAs, which might be regulated by miRNAs, have crucial roles in many cancers. However, the miRNA-dependent crosstalk between lncRNA and mRNA in specific MIBC subtypes still remains unclear. In this study, we first classified MIBC into two conservative subtypes using miRNA, mRNA and lncRNA expression data derived from The Cancer Genome Atlas. Then we investigated subtype-related biological pathways and evaluated the subtype classification performance using Decision Trees, Random Forest and eXtreme Gradient Boosting (XGBoost). At last, we explored potential miRNA-mediated lncRNA-mRNA crosstalks based on co-expression analysis. Our results show that: (1) the luminal subtype is primarily characterized by upregulation of metabolism-related pathways while the basal subtype is predominantly characterized by upregulation of epithelial-mesenchymal transition, metastasis, and immune system process-related pathways; (2) the XGBoost prediction model is consistently robust for classification of the molecular subtypes of MIBC across four datasets (The area under the ROC curve>0.9); (3) the expression levels of the molecules in the miR-200c and miR141-mediated lncRNA-mRNA crosstalks differ considerably between the two subtypes and have close relationships with the prognosis of MIBC. The miR-200c and miR-141-dependent mRNA-lncRNA crosstalks might be of great significance in tumorigenesis and tumor progression and may serve as the novel prognostic predictors and classification markers of MIBC subtypes.

Keywords: MiR200c, miR-141, random forest (RF), XGBoost, subtypes, Muscle-invasive bladder cancer (MIBC)

Received: 15 Jun 2018; Accepted: 10 Sep 2018.

Edited by:

Quan Zou, Tianjin University, China

Reviewed by:

Leyi Wei, Tianjin University, China
Chi Zhang, School of Medicine, Indiana University Bloomington, United States
Qing Li, Huntsman Cancer Institute, University of Utah, United States  

Copyright: © 2018 Liu, Chen, Danilova, Bolkov, Tuzankina and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Guojun Liu, Ural Federal University, Yekaterinburg, Russia, 303494808@qq.com