Dados do Trabalho

Título

ABORDAGEM IN SILICO E PROTEOMICA SUGERE REGULAÇAO AUMENTADA DE MIR-146-5P EM TNBC E MODULAÇAO DE PROTEINAS CRITICAS

Título em Inglês

IN SILICO AND PROTEOMICS APPROACHES SUGGEST UPREGULATION OF miR-146a-5p IN TNBC AND MODULATION OF CRITICAL PROTEINS.

Introdução

Breast cancer (BC) is the most common cancer type after non-melanoma skin tumors among Brazilian women, with 61.61 cases estimated for 100 thousand women in 2020. New biomarkers, such as miRNAs and selected proteins, are essential in personalized medicine.

Objetivos

To evaluate the expression and possible role of miR-146a-5p in subtypes of BC.

Métodos

miRNAs selection was performed using in silico analysis from the TCGA database. Data from the miRNAs expression of 1085 patients were accessed and compared among BC subtypes. After normalization, the Bayesian Student t-test evaluated differential expression (DE) analysis via the limma R package. Lists with DE miRNAs were divided between up and down-regulated status (FC = ±2). A second approach was to submit the data obtained from BC samples´ mass spectrometry to IPA software to predict the activation/inhibition of upstream regulators in DE proteins lists in the tumor (T) versus contralateral tissue (CT).

Resultados

A total of 206 upstream regulators were discovered at p<0.05; 12.6% of them were predicted with z-score values. In TCGA analysis, miR-146a-5p was found up-regulated in triple-negative (TNBC) in comparison to other subtypes as a hormonal receptor (HR)+, HER2+, and non-TNBC (HR+ plus HER2+). The same was observed in TNBC cell lines by RT-qPCR. This miRNA was also predicted as an indirect regulator of CAT, LTF, CFH, and PGLYRP2 proteins in IPA analysis. The proteomic analysis also demonstrated these molecules´ relation with cancer hallmarks such as invasion, inflammation, and immune response.

Conclusões

The results suggest that miR-146a-5p deregulation has a role in BC, mainly in TNBC, via the regulation of essential proteins. A better understanding of these molecules in BC is critical to define new biomarkers.

Palavras Chave

breast cancer, miR-146a-5p, protein analysis, biomarker.

Área

TUMOR CELL, MOLECULAR BIOLOGY, PREDICTIVE AND PROGNOSTIC FACTORS - Genetics