miR-452 Function in Breast Cancer

Abstract

Background: Breast cancer is the most frequently diagnosed life-threatening cancer in women. Young Lebanese women have a higher prevalence of breast cancer as compared to their counterparts in western countries. Various hereditary and environmental factors contribute to the initiation and the progression of the disease. microRNAs (miRNAs) have been shown to play a critical role in the development and the progression of breast cancer and other types of cancer. miRNAs, a class of endogenous small noncoding RNAs that are approximately 18-22 nucleotides in length, function as oncogenes and tumor suppressor genes and are essential for the post transcriptional regulation of mRNA gene expression. Recent data in our lab has shown that miR-452 is significantly downregulated in tumor tissues taken from young Lebanese breast cancer patients as compared to normal adjacent tissues upon performing miRNA microarray. Aim: Our project aims at studying the role of miR-452 in breast cancer through investigating its potential target genes (WWP1, CDKN1B, HECTD1, SOX7 and BMI1) that were derived based on PubMed search, experimentally validated and predicted in silico tools. Methods: The expression of miR-452 in breast cancer cell lines was measured by Reverse Transcription Quantitative Real Time PCR (RT-qPCR). The level of relative expression of target genes in MCF-cells was validated by RT-qPCR. Modulation of miR-452 expression in MCF-7 cells was done by transfecting miR-452 mimics. MTT assay, Trypan Blue Dye Exclusion Assay and Invasion Assay were used to check for the effect of overexpression of miR-452 on proliferation, viability and invasion in transfected cells. Results: miR-452 was significantly downregulated in all tested breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-453, BT-474). A strongly significant downregulation of miR-452 was seen in MCF-7 cells which are hormone positive and have similar profile to the young Lebanese breast cancer patients. Overexpression of miR-452 decreased the mRNA levels of target genes. N