Abstract
Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, wherein diagnostic limitations and lack of accurate prognostic factors are important clinical challenges. In this study, we report the discovery of 234 novel miRNAs in non-neoplastic thyroid and PTC samples, obtained from publicly available small RNA sequencing datasets (TCGA and GEO). These sequences were observed to display similar molecular features compared to currently annotated miRNAs. These potentially novel miRNAs presented tissue-specificity and largely decreased expression in PTC compared to non-neoplastic samples. We showed that the disrupted novel miRNAs have diagnostic and prognostic potential, and were associated with BRAF mutation, a frequent alteration related to more aggressive PTC. In conclusion, our results expand the miRNA repertoire in thyroid tissues and highlight the potential biological role and clinical utility of previously unannotated miRNAs.
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Durante C, Grani G, Lamartina L, Filetti S, Mandel SJ, Cooper DS. The diagnosis and management of thyroid nodules: a review. JAMA. 2018;319:914–24.
Lamartina L, Grani G, Durante C, Borget I, Filetti S, Schlumberger M. Follow-up of differentiated thyroid cancer - what should (and what should not) be done. Nat Rev Endocrinol. 2018;14:538–51.
Fagin JA, Wells SA. Biologic and clinical perspectives on thyroid cancer. N Engl J Med. 2016;375:1054–67.
Eszlinger M, Lau L, Ghaznavi S, Symonds C, Chandarana SP, Khalil M, et al. Molecular profiling of thyroid nodule fine-needle aspiration cytology. Nat Rev Endocrinol. 2017;13:415–24.
Gebert LFR, MacRae IJ. Regulation of microRNA function in animals. Nat Rev Mol Cell Biol. 2019;20:21–37.
Minatel BC, Martinez VD, Ng KW, Sage AP, Tokar T, Marshall EA, et al. Large-scale discovery of previously undetected microRNAs specific to human liver. Hum Genomics. 2018;12:16.
Sage AP, Minatel BC, Marshall EA, Martinez VD, Stewart GL, Enfield KSS, et al. Expanding the miRNA transcriptome of human kidney and renal cell carcinoma. Int J Genom. 2018;2018:6972397.
Londin E, Loher P, Telonis AG, Quann K, Clark P, Jing Y, et al. Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs. Proc Natl Acad Sci USA. 2015;112:E1106–15.
An J, Lai J, Lehman ML, Nelson CC. miRDeep*: an integrated application tool for miRNA identification from RNA sequencing data. Nucleic Acids Res. 2013;41:727–37.
Fehlmann T, Backes C, Kahraman M, Haas J, Ludwig N, Posch AE, et al. Web-based NGS data analysis using miRMaster: a large-scale meta-analysis of human miRNAs. Nucleic Acids Res. 2017;45:8731–44.
Mogilyansky E, Rigoutsos I. The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease. Cell Death Differ. 2013;20:1603–14.
Hamilton MP, Rajapakshe K, Hartig SM, Reva B, McLellan MD, Kandoth C, et al. Identification of a pan-cancer oncogenic microRNA superfamily anchored by a central core seed motif. Nat Commun. 2013;4:2730.
Lin S, Gregory RI. MicroRNA biogenesis pathways in cancer. Nat Rev Cancer. 2015;15:321–33.
Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.
Yuan X, Mu N, Wang N, Strååt K, Sofiadis A, Guo Y, et al. GABPA inhibits invasion/metastasis in papillary thyroid carcinoma by regulating DICER1 expression. Oncogene. 2018;38:965–79.
Xing M, Alzahrani AS, Carson KA, Shong YK, Kim TY, Viola D, et al. Association between BRAF V600E mutation and recurrence of papillary thyroid cancer. J Clin Oncol. 2015;33:42–50.
Shen X, Zhu G, Liu R, Viola D, Elisei R, Puxeddu E, et al. Patient age-associated mortality risk is differentiated by BRAF V600E status in papillary thyroid cancer. J Clin Oncol. 2018;36:438–45.
Beltrami CM, Dos Reis MB, Barros-Filho MC, Marchi FA, Kuasne H, Pinto CAL, et al. Integrated data analysis reveals potential drivers and pathways disrupted by DNA methylation in papillary thyroid carcinomas. Clin Epigenetics. 2017;9:45.
Ortiz IMDP, Barros-Filho MC, Dos Reis MB, Beltrami CM, Marchi FA, Kuasne H, et al. Loss of DNA methylation is related to increased expression of miR-21 and miR-146b in papillary thyroid carcinoma. Clin Epigenetics. 2018;10:144.
Acknowledgements
This work was supported by grants from the Canadian Institutes for Health Research (CIHR FDN-143345) and the São Paulo Research Foundation (FAPESP 2015/20748-5). MCBF are supported by scholarships from FAPESP (2015/17707-5 and 2018/06138-8). BCM, APS, EAM and VDM are supported by scholarships from the University of British Columbia. APS, EAM and LDR are also supported by scholarships from CIHR. EAM is a Vanier Canada Graduate Scholar.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Barros-Filho, M.C., Pewarchuk, M., Minatel, B.d.C. et al. Previously undescribed thyroid-specific miRNA sequences in papillary thyroid carcinoma. J Hum Genet 64, 505–508 (2019). https://doi.org/10.1038/s10038-019-0583-7
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/s10038-019-0583-7
This article is cited by
-
Profiling the small non-coding RNA transcriptome of the human placenta
Scientific Data (2021)