Title: mir-29b Inhibits proliferation and induces apoptosis in triple negative breast cancer cells
Abstract:
Triple negative breast cancer (TNBC) is a particular breast cancer subtype, with the worse prognostic, characterised by the lack of expression of progesterone, estrogen and Her2 protein.
Alterations of condign and non-coding genes were observed, a particular attention received short non-coding RNAs transcripts, also called microRNAs (miRNAs). Among this class, captured attention a transcript overexpressed in TNBC and correlated with the overall survival rates, as revealed TCGA data.
The aim of our study was to investigate the mechanistic role of miR-29b in TNBC, by using a miRNA inhibitor for this transcript, followed by evaluation the cellular and molecular effects on TNBC cells. A model for TNBC was selected BT549 and MDA-MB-231 cells, overexpressing miR-29b.
In the case of transient inhibition of this transcript, on selected cell lines was observed a decreased cell proliferation rate and colony number. The fluorescence microscopy tests revealed activation of apoptosis and autophagy. Additional to this functional test, important alterations were observed at transcriptomic level, microarray evaluation revealed 8 upregulated and 11 downregulated miRNAs in BT549 cells, and 33 upregulated and 10 downregulated miRNAs in MDA-MB-231 cells in the group transfected with miR-29b versus negative control group. Additional validation by qRT-PCR of the main target genes revealed overexpression of two important genes that promote the resistance to therapy (MCL1 and BCL2).
miR-29b-3p inhibited proliferation and induced apoptosis and autophagy, the molecular mechanism being complex; our data emphasis the activation of the mechanisms responsible for resistance to therapy.
Acknowledgement: This study was financed by PCE grant “Testing small molecule targeting mitogen activated protein kinases: Successes, challenges and opportunities in triple negative breast cancer systems- ORIENT”.
