Tumor Suppressor miR-27a-5p and Its Significance for Breast Cancer

Tumor Suppressor miR-27a-5p and Its Significance for Breast Cancer

Background: MicroRNAs are well established as master regulators of carcinogenesis and potential biomarkers in breast cancer (BC). In a preliminary effort, we found miR-27a-5p to be significantly downregulated in experimentally derived mammospheres and BC patients from The Cancer Genome Atlas Breast...

Full description

Saved in:
Bibliographic Details
Published in:Biomedicines Vol. 12; no. 11; p. 2625
Main Authors: Parrella, Paola, Barbano, Raffaela, Jonas, Katharina, Fontana, Andrea, Barile, Serena, Rendina, Michelina, lo Mele, Antonio, Prencipe, Giuseppina, Ciuffreda, Luigi, Morritti, Maria Grazia, Valori, Vanna Maria, Graziano, Paolo, Maiello, Evaristo, Copetti, Massimiliano, Pichler, Martin, Pasculli, Barbara
Format: Journal Article
Language:English
Published: Basel MDPI AG 17-11-2024
MDPI
Subjects:
Biomarkers
Breast cancer
Breast carcinoma
Cancer therapies
Carcinogenesis
Cell migration
Cell proliferation
Efficiency
Estrogens
Gene expression
Invasiveness
Metastases
Metastasis
MicroRNAs
miRNA
Phenotypes
Reagents
Surgery
Tissues
Tumor suppressor genes
Tumors
Wound healing
United States > US
Germany
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background: MicroRNAs are well established as master regulators of carcinogenesis and potential biomarkers in breast cancer (BC). In a preliminary effort, we found miR-27a-5p to be significantly downregulated in experimentally derived mammospheres and BC patients from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) dataset. Objectives. Herein, we sought to investigate the putative involvement of miR-27a-5p in promoting a migratory phenotype of breast cancer cells, and establish whether miR-27a-5p is associated with patient clinicopathological characteristics. Methods: miR-27a-5p capability of inducing a metastasis-prone cell phenotype was analyzed in SUM159 and MDA-MB-231, both representing the triple negative BC subtype. miR-27a-5p expression profile was carried out in a cohort of 232 BC patients and normal breast tissues (NBTs) by RT-qPCR. Results: Transient miR-27a-5p inhibition did not affect cell proliferation but led to a significant increase of cell migration in knocked-down compared to control cells. Following quantification in the patient cohort, miR-27a-5p was found higher in NBTs (Median 2.28, IQR 1.50–5.40) and pre-invasive breast lesions (Median 3.32, IQR 1.68–4.32) compared to tumors. In particular, miR-27a-5p was less expressed in patients with synchronous (Median 1.03, IQR 0.83–1.58) or metachronous (Median 1.83, IQR 1.29–3.17) metastases than in patients free from metastases after a 5-year follow-up (Median 2.17, IQR 1.19–3.64), suggesting that miR-27a-5p expression is negatively correlated with breast pathology evolution (R = −0.13, p = 0.038). However, time-to-event analysis did not highlight significant associations with patient outcome in either our internal cohort or TCGA-BRCA dataset. Conclusions: Our study suggests a potential role of miR-27a-5p as tumor suppressor miRNA in breast cancer. Further investigations may help define its biomarker potential in each breast cancer subtype, and identify other molecular partners as targets for new interventions.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines12112625