Small non-coding RNA as master regulators in thyroid cancer

• Grant number: 18/06138-8
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: August 01, 2018
• End date: July 31, 2019
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Luiz Paulo Kowalski
• Grantee: Mateus de Camargo Barros Filho
• Supervisor: Wan L. Lam
• Host Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil
• Institution abroad: BC Cancer Agency, Canada
• Associated to the scholarship: 15/17707-5 - Development of molecular procedures useful for differential diagnosis in thyroid nodules, BP.PD

Abstract

The differential diagnosis of thyroid nodules is challenging, and many patients are submitted to unnecessary surgical procedures. During the post-doctoral period, we developed a diagnostic algorithm based on DNA methylation (bisulfite pyrosequencing) and tested an mRNA-based tool (RT-qPCR) in biopsies of thyroid lesions. Additionally, we characterized microRNAs (miRNAs) potentially regulated by DNA methylation in papillary thyroid carcinoma (PTC). The objective of this BEPE internship is to further explore the small non-coding RNA (sncRNA) role and its potential use in thyroid cancer diagnosis in collaboration with Dr Wan L. Lam, British Columbia Cancer Research Centre, Vancouver, Canada. Dr. Lam's group has expertise and strong background in non-coding RNA and bioinformatics in different tumor types. This knowledge added to our previous molecular data in thyroid cancer has strong potential to unveil highly specific sncRNA in these lesions (novel and already described) using sequencing data from public database (TCGA). As we are currently extracting both DNA and total RNA from fine needle aspiration biopsies (FNAB) slides with undetermined results, we intent to design a new diagnostic molecular tool assessing sncRNA, since this is a very stable RNA fraction that can be readily measured in our archived samples. Furthermore, we intend to use and improve a methodology that we implemented to identify "master regulator" miRNAs, allowing the detection of the most impactful miRNA in the disruption of the PTC transcriptome. In vitro experiments using miRNA mimics and antagomiRs will be also conducted to corroborate this strategy, which can be useful to develop novel therapies based on miRNA inhibition. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ROCK, LEIGHA D.; MINATEL, BRENDA C.; MARSHALL, ERIN A.; GUISIER, FLORIAN; SAGE, ADAM P.; BARROS-FILHO, MATEUS CAMARGO; STEWART, GREG L.; GARNIS, CATHIE; LAM, WAN L.. Expanding the Transcriptome of Head and Neck Squamous Cell Carcinoma Through Novel MicroRNA Discovery. FRONTIERS IN ONCOLOGY, v. 9, NOV 27 2019. (18/06138-8)

PEWARCHUK, MICHELLE E.; BARROS-FILHO, MATEUS C.; MINATEL, BRENDA C.; COHN, DAVID E.; GUISIER, FLORIAN; SAGE, ADAM P.; MARSHALL, ERIN A.; STEWART, GREG L.; ROCK, LEIGHA D.; GARNIS, CATHIE; et al. Upgrading the Repertoire of miRNAs in Gastric Adenocarcinoma to Provide a New Resource for Biomarker Discovery. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 20, n. 22, NOV 2019. (18/06138-8)

COHN, DAVID E.; BARROS-FILHO, MATEUS C.; MINATEL, BRENDA C.; PEWARCHUK, MICHELLE E.; MARSHALL, ERIN A.; VUCIC, EMILY A.; SAGE, ADAM P.; TELKAR, NIKITA; STEWART, GREG L.; JURISICA, IGOR; et al. Reactivation of Multiple Fetal miRNAs in Lung Adenocarcinoma. CANCERS, v. 13, n. 11, JUN 2021. (18/06138-8)

GUISIER, FLORIAN; BARROS-FILHO, MATEUS CAMARGO; ROCK, LEIGHA D.; STRACHAN-WHALEY, MEGAN; MARSHALL, ERIN A.; DELLAIRE, GRAHAM; LAM, WAN L.; BIRBRAIR, A. Janus or Hydra: The Many Faces of T Helper Cells in the Human Tumour Microenvironment. TUMOR MICROENVIRONMENT: HEMATOPOIETIC CELLS, PT A, v. 1224, p. 17-pg., 2020-01-01. (18/06138-8, 15/17707-5)

BARROS-FILHO, MATEUS CAMARGO; PEWARCHU, MICHELLE; MINATEL, BRENDA DE CARVALHO; SAGE, ADAM P.; MARSHALL, ERIN A.; MARTINEZ, VICTOR D.; ROCK, LEIGHA D.; MACAULAY, GAVIN; KOWALSKI, LUIZ PAULO; ROGATTO, SILVIA REGINA; et al. Previously undescribed thyroid-specific miRNA sequences in papillary thyroid carcinoma. JOURNAL OF HUMAN GENETICS, v. 64, n. 5, p. 505-508, MAY 2019. (18/06138-8, 15/17707-5, 15/20748-5)