Differential Expression Profiles Of MicroRNAs In Breast Cancer Cell Lines And The Effect Of Hsa-miR-340 To Breast Cancer Cell Invasion Potential

Background MicroRNAs (miRNAs or miRs) are conserved, single-stranded, 18-24 nucleotide non-protein-coding RNAs,and they regulate protein expression at post-transcriptional level. MicroRNAs have quite recently emerged as a novel class of gene regulators, which play important roles in many biological processes, including embryonic development, fat metabolism, cell growth, differentiation and apoptosis, and gene regulation. Accelerating research has resulted in some miRNA has took part in the tumorigenesis, invasion and metastasis of human breast cancer. Although alterations of miRNAs in human cancers have been reported, the biological functions of miRNAs are not yet fully understood. Objective To investigate the expression of hsa-miRNAs change in the breast cancer cell lines with differing invasiveness; To investigate the effect of miR-340 to breast cancer cell invasion potential, and to predict potential targets of miR-340. Method (1) To explore differential expression of miRNAs between breast cancer cell line MCF-7 and MDA-MB-231 by miRNA array. (2) The expression of miR-340 in different breast cancer cell lines (MDA-MB-231, MDA-MB-468 and MCF-7) was detected by QRT-PCR. (3) hsa-miR-340 inhibitors was transfected into breast cancer cell line MCF-7 to reduce the activity of miR-340. The impact of miR-340 downregulation on proliferation and invasion potential were evaluated by CCK-8 kit and invasion assay. The possible target genes of miR-340 were forecasted by bioinformatics tools. (4) The possible target genes of miRNA-340 were forecasted by bioinformatics tools. Results (1) There were 112 altered miRNAs between breast cancer cell line MCF-7 and MDA-MB-231.Compared with breast cancer cell line MDA-MB-231 , there were 34 kinds of miRNAs altered significantly in breast cancer cell line MCF-7,of which 14 miRNAs were upregulated (hsa-miR-340,miR-335,miR-126,et al), 20 miRNAs were downregulated( hsa-miR-186,hsa-miR-125b -1*,et al). (2) The results of QRT-PCR showed that the expression of miR-340 was upregulated significantly in the lower invasion potential breast cell line MCF-7 compared with higher invasion potential breast cancer cell lines MDA-MB-231 and MDA-MB-468 (P<0.05). (3) Transfected cells showed a higher invasion potential than untransfected cells as miR-340 had been downregulated (P<0.05), but the proliferation has no significantly change (P>0.05). (4) Using bioinformatics tools, saveral possible target genes of miRNA-340 were forecasted, including CTNNB, ZNF403 and CCPG1. Conclusion (1) The altered expression of miRNAs exist in the breast cancer cell lines with different invasive ability. (2) MiR-340 may negatively regulate the invasiveness possible of breast cancer cells, and cancer cells showed a higher invasion potential after the activity of miR-340 was reduced. (3) MiR-340 play important roles in carcinogenesis and cancer progression by regulating the possible target genes.