Effect of SMYD3 on the microRNA expression profile of MCF-7 breast cancer cells

Abstract

Abstract. SET and MYND domain containing 3 (SMYD3) is a histone methyltransferase (HMT) and transcription factor, which serves important roles in carcinogenesis. Numerous downstream target genes of SMYD3 have been identified in previous studies. However, the downstream microRNA (miRNA) s regulated by SMYD3 are yet to be elucidated. In the present study, the results of miRNA microarray demonstrated that 30 miRNA expression profiles were upregulated, whilst 24 miRNAs were downregulated by >2.0-fold in the SMYD3-overexpressed MCF-7 breast cancer cells. The HMT activity was demonstrated to be essential for SMYD3-mediated transactivation of miR-200c-3p and the overexpression of miR-200c-3p inhibited the transactivation effects of SMYD3 on myocardin-related transcription factor-A-dependent migration-associated genes. To our best knowledge, the current study is the first to report on the transcriptional regulation of SMYD3 on miRNAs, and miR-200c may be a downstream negative regulator of the SMYD3-mediated pathway in the migration of breast cancer cells. These results may provide a novel theoretical basis to understand the mechanisms underlying the initiation, progression, diagnosis, prevention and therapy of breast cancer. IntroductionSET and MYND domain containing 3 (SMYD3) is a novel histone methyltransferase gene identified in hepatoma and colon carcinoma cells by Hamamoto et al (1). SMYD3 is located on human chromosome 1 and encodes two protein isoforms that are composed of 428 and 369 amino acids. Previous studies have demonstrated that SMYD3 is frequently overexpressed in numerous types of cancer cells, including hepatic, colon, gastric and cervical carcinoma, and breast cancer (2-4), whilst the expression levels were lower in the corresponding normal tissue. A number of previous studies have demonstrated that SMYD3 has vital roles in the process of tumor development via its functions as a histone methylation enzyme and a transcription factor (5,6). SMYD3 modifies chromatin structure by catalyzing the methylation of histone H3 at lysine 4 (H3K4), H4K20 and H4K5 (5,6). Also, SMYD3 regulates the transcription of target genes via associating with RNA polymerase II or HELZ RNA helicase and binding at the motif CCCTCC or GGAGGG in the promoter (1).MicroRNAs (miRNAs) are small, non-coding, endogenous RNA molecules of 18-22 nucleotides that were first identified in Caenorhabditis elegans. miRNAs suppress gene expression by binding the targeted mRNA transcripts, which causes translational repression or mRNA degradation. Previous studies demonstrated that miRNAs serve important roles in tumorigenesis through the regulation of genes involved in cancer development and maintenance (7,8).A number of studies have identified that histone methylation and miRNAs are essential in the initiation and progression of cancer (7-9). However, the association between SMYD3 and miRNAs is yet to be elucidated. To investigate this further, the current study analyzed the global regulatory effects of SMYD3 on miRNAs in breast cancer cells usi...

Analysis of change in microRNA expression profiles of lung cancer A549 cells treated with Radix tetrastigma hemsleyani flavonoids

“… 24 – 26 Upregulation of miR-146a-3p may target some TSGs and inhibit OGs to inhibit the proliferation of A549 cells treated with RTHF. As tumor suppressor miRNA, hsa-miR-4792 downregulated in uterine leiomyoma, breast cancer, and nasopharyngeal carcinoma 27 – 30 was the second most overexpressed miRNA in RTHF-treated A549 cells; it has been reported that overexpression of hsa-miR-4792 can inhibit epithelial–mesenchymal transition and invasion in nasopharyngeal carcinoma by inhibiting FOXC1, which is a critical mediator of EGFR function in human cancer. 27 hsa-miR-4792 was most abundantly increased in glioblastoma multiforme (GBM) when GBM cells are exposed to necrotic cells 31 and was most abundantly expressed in human adipose mesenchymal stem cell-derived conditioned medium (hAMSC-CM) treatment ovarian cancer cells and may be involved in the inhibitory influence of hAMSC-CM toward ovarian cancer cell.…”

Differential Regulation of circRNA, miRNA, and piRNA during Early Osteogenic and Chondrogenic Differentiation of Human Mesenchymal Stromal Cells

“…With dexamethasone controlling SMYD3 transcript formation at least in pellet culture, the overall transcript downregulation appears to be associated to a higher expression of miR-181a-5p, miR-181b-5p, and miR-671-5p (as identified from RNAseq). However, since SMYD3 protein has been associated to a specific transcriptional regulation of miRNA [72], whether this association is by a diminished miRNA sponging activity or not has yet to be demonstrated.…”

Correlations of EZH2 and SMYD3 gene polymorphisms with breast cancer susceptibility and prognosis

“…A previous study also found that high expression of EZH2 was associated with poor outcome in breast cancer [ 30 ]. SMYD3, a histone methyltransferase, played an important role in transcriptional regulation in human carcinogenesis [ 31 ]. High SMYD3 expression was critical for the development of breast cancer cells [ 32 ].…”