Abstract
BackgroundMicroRNAs are small RNAs (~ 22 nt) that modulate the expression of thousands of genes in tumors and play important roles in the formation of multidrug resistance. In this study, we firstly investigated that miR-4532 involved in the multidrug resistance formation of breast cancer by targeting hypermethylated in cancer 1 (HIC-1), a tumor-suppressor gene.MethodsTo identify and characterize the possible miRNAs in regulating multidrug resistance, we employed the transcriptome sequencing approach to profile the changes in the expression of miRNAs and their target mRNAs were obtained by bioinformatics prediction. Then the molecular biology experiments were conducted to confirm miR-4532 involved in multidrug resistance formation of breast cancer.ResultsThe luciferase reporter assay experiment was employed to confirm that HIC-1 was the target of miR-4532. Transfection with an miR-4532 mimic indicated miR-4532 mimic significantly increased breast cancer cell resistance to adriamycin. Cell proliferation and invasion assay experiments showed overexpression of HIC-1 inhibited the invasion and metastasis of breast cancer cells. Meanwhile, the interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) signaling pathway was confirmed to be involving in multidrug resistance by western blotting experiments.ConclusionsThese results suggest that downregulation of hypermethylated in cancer-1 by miR-4532 could promote adriamycin resistance in breast cancer cells, in which the IL-6/STAT3 pathway was regulated by the HIC-1. This finding might contribute to new therapeutic target for reversal of tumor resistance.
Highlights
MicroRNAs are small RNAs (~ 22 nt) that modulate the expression of thousands of genes in tumors and play important roles in the formation of multidrug resistance
gene ontology (GO) analysis was performed to determine the physiological roles of these target genes (Fig. 1), and the results indicated that these target genes were mainly
The results showed that miR-4532, miR-30b, and miR-30c expression levels were similar to those in MCF-7 cells. miR-30b and miR-30c have been reported in prior studies of cancer drug resistance
Summary
MicroRNAs are small RNAs (~ 22 nt) that modulate the expression of thousands of genes in tumors and play important roles in the formation of multidrug resistance. We firstly investigated that miR-4532 involved in the multidrug resistance formation of breast cancer by targeting hypermethylated in cancer 1 (HIC-1), a tumor-suppressor gene. One miRNA can modulate hundreds of target genes, and one gene can be repressed by hundreds of miRNAs [7, 8] These miRNAbased pathways have been shown to regulate cell proliferation, migration and programmed cell death, including apoptosis and autophagy, in cancer cells [9,10,11,12]. Several miRNAs, including miR-27, have been shown to be involved in MDR in cancer [19], through modulation of apoptosis and autophagy pathways
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