Effects of human endogenous microRNAs on the repertoire of cancer stem cells and Cancer progression using Zebrafish as in vivo model

• Grant number: 17/22312-5
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): March 01, 2018
• Effective date (End): January 31, 2022
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal researcher: Deilson Elgui de Oliveira
• Grantee: Barbara Grasiele Muller Coan
• Home Institution: Instituto de Biotecnologia (IBTEC). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Cancers are neoplastic malignancies of multifactorial origin that typically occur in adults, being most often carcinomas. The process of Cancer development, carcinogenesis, is divided into three stages: initiation, promotion and progression. It is during progression that usually the detection of the disease occur and its onset is characterized by the acquisition of the cell malignant phenotype (cell transformation). Transformed cells can acquire many properties (e. g., autonomy in the generation of pro-proliferative stimuli and vascular remodeling) that provide conditions for the dissemination of neoplastic cells to sites distant from the primary site, in a process called metastasis. For metastasis establishment, it is necessary to modify the tumor microenvironment of this new site, so that the newcomer cells survive and proliferate. This microenvironment favors the appearance and suffers the influence of so-called Cancer Stem Cells (CSCs) that play a fundamental role in the establishment and maintenance of metastasis. Gene regulation of tumor cells and modulation of CSCs is due in part to the influence of epigenetic factors, among them microRNAs (miRNAs or miRs). miRs cans influence various cellular processes, including carcinogenesis and tumor progression. In a recent study by our research group, we observed that nasopharyngeal immortalized cells (NP69) had an upregulation of miR-100-5p, miR-192-5p and miR-574-3p when transfected with latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) from the M81 variant compared to the LMP1 B95-8A variant. Based on the in silico prediction analysis of the miRs targets, we identified that they could provide changes in intracellular signaling pathways related to cell survival, cell proliferation, apoptosis and angiogenesis. However, the findings of this study require further functional analysis of the effects of these miRs and their importance in the progression of Human Cancers. For these reasons, this study aims to investigate whether these miRs play an important role in cell survival, proliferation, migration and invasion, repertoire of cells expressing CSCs markers, tumorigenesis and metastasis formation using in vitro assays and in vivo experimentation in Zebrafish model. (AU)

Scientific publications

(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)

CAETANO, BRUNNO FELIPE R.; JORGE, BEATRICE ADRIANNE S.; MUELLER-COAN, BARBARA GRASIELE; DE OLIVEIRA, DEILSON ELGUI. Epstein-Barr virus microRNAs in the pathogenesis of human cancers. Cancer Letters, v. 499, p. 14-23, FEB 28 2021. Web of Science Citations: 1.