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Study the role of microRNA in cancer metastasis using genetically engineered mouse models

Grant number: 17/01829-0
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): May 01, 2017
Effective date (End): April 30, 2018
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Edna Teruko Kimura
Grantee:Cesar Seigi Fuziwara
Supervisor abroad: Lin He
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : University of California, Berkeley (UC Berkeley), United States  
Associated to the scholarship:14/50521-0 - Transcriptional regulation of miR-17-92 microRNA in aggressive thyroid cancer, BP.PD

Abstract

miRNA deregulation is an important step in oncogenesis associated with activation of oncogenic pathway and inhibition of tumor-suppressor genes. During tumor progression, a complex network of miRNAs and its targets are modulated which is likely to contribute to metastatic phenotype and tumor spreading. Metastases are the main cause of cancer-related death, particularly lung cancer, which is the most prevalent cancer type in the USA. Therefore, investigating the function of miRNAs in tumor metastasis will provide important insights in tumor biology and potentially lead to therapy that will improve the overall survival rate. miR-200 family comprises five miRNA members located at two genomic loci. miR-200s has been extensively studied for their role in regulating epithelia-to-mesenchymal transition (EMT). However, the role of miR-200s in regulating tumor metastasis remain controversial. As tumor metastases is a complex multi-step cascade involving local invasion, intravasation, survival in the circulation, extravasation and colonization, to study the role of miR-200s in each step during the process, it is important to use an in vivo model which can develop spontaneous tumor metastases to capture all the steps. In this study, we aim to investigate the role of miR-200 family in lung cancer metastasis using genetically engineered lung cancer mouse model (KrasLSL-G12D/+;p53flox/flox), We will perform loss of function experiment using CRISPR/Cas9 genome editing in vivo to uncover the role of miR-200 family during tumor progression.