title: MicroRNA-mediated networks underlie immune response regulation in papillary thyroid carcinoma.
abstract: Papillary thyroid carcinoma (PTC) is a common endocrine malignancy with low death rate but increased incidence and recurrence in recent years. MicroRNAs (miRNAs) are small non-coding RNAs with diverse regulatory capacities in eukaryotes and have been frequently implied in human cancer. Despite current progress, however, a panoramic overview concerning miRNA regulatory networks in PTC is still lacking. Here, we analyzed the expression datasets of PTC from The Cancer Genome Atlas (TCGA) Data Portal and demonstrate for the first time that immune responses are significantly enriched and under specific regulation in the direct miRNA--target network among distinctive PTC variants to different extents. Additionally, considering the unconventional properties of miRNAs, we explore the protein-coding competing endogenous RNA (ceRNA) and the modulatory networks in PTC and unexpectedly disclose concerted regulation of immune responses from these networks. Interestingly, miRNAs from these conventional and unconventional networks share general similarities and differences but tend to be disparate as regulatory activities increase, coordinately tuning the immune responses that in part account for PTC tumor biology. Together, our systematic results uncover the intensive regulation of immune responses underlain by miRNA-mediated networks in PTC, opening up new avenues in the management of thyroid cancer.
authors.affiliation: Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
authors.forename: Chen-Tsung
authors.initials: CT
authors.lastname: Huang
authors.affiliation: Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
authors.forename: Yen-Jen
authors.initials: YJ
authors.lastname: Oyang
authors.affiliation: Institute of Biomedical Informatics and Center for Systems and Synthetic Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hsuan-Cheng
authors.initials: HC
authors.lastname: Huang
authors.affiliation: 1] Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan [2] Department of Life Science, National Taiwan University, Taipei, Taiwan [3] Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan.
authors.forename: Hsueh-Fen
authors.initials: HF
authors.lastname: Juan
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D002291:Carcinoma, Papillary; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012333:RNA, Messenger