CRITICAL ROLE OF MIR-877-5P IN PROLIFERATION AND ADHESION OF TRIPLE NEGATIVE BREAST CANCER

GRINPELC, AGUSTINA; MORO, JUANA; GRAÑA, KAREN; VERA-SÁNCHEZ, LEANDRO; SCALICE, GEORGINA; PICCIONI, FLAVIA VALERIA; VERDE ARBOCCO, FIORELLA; DE SIERVI, ADRIANA; DE LUCA, PAOLA

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAB AAFE AACYTAL 2023; 2023

SAIC SAB AAFE AACYTAL

Breast cancer (BC) is the leading cause of cancer death in women. Triple negative breast cancer (TNBC) is the molecular subtype that is known for having a poor prognosis and limited therapeutic options compared to other subtypes of BC. MiRNAs are small non-coding RNAs that regulate gene expression. Aberrant expression of miRNAs in body tissues and fluids are linked to pathologies such as BC. Previously, we identified several miRNAs whose expression is altered in BC tissue and correlates with patient survival using bioinformatic approaches. In particular, we found that miR-877-5p was diminished in BC tissue compared to normal adjacent tissue (NAT) and its expression correlates with worse overall survival. The aim of this work was to investigate the effect of miR-877-5p in TNBC experimental models. Our hypothesis is that miR-877-5p has oncogenic functions in TNBC increasing tumor growth and progression. We first determined miR-877-5p expression levels in PAM50 basal-like BC tumors and NAT of patients from the TCGA BRCA data set. The miR-877-5p was significantly increased in PAM50 basal-like BC tissue compared to normal adjacent tissue. Analysis using UCSC Xena tool showed that its expression is increased in basal-like BC compared to the other PAM50 BC molecular subtypes. To investigate the effect of miR-877-5p in TNBC, we generated 4T1 stable-transfected cells with this miRNA overexpressed or control cells after cloning miR-877-5p into plasmid vector. Additionally, transient transfections with miRNA inhibitors were performed. Then, we evaluated the effect of miR-877-5p in proliferation, adhesion and migration of 4T1 cells through in vitro assays. We found that miR- 877-5p inhibitor decreased cell viability and adhesion in this BC cell line. Our results suggest that targeting miR-877-5p could have potentialtherapeutic implications by impairing the survival and adhesive properties of 4T1 tumor cells, thereby potentially limiting their ability to spread and proliferate.