Effects of siRNA-Mediated Knockdown of HDAC1 on the Biological Behavior of Esophageal Carcinoma Cell Lines
نویسندگان
چکیده
BACKGROUND HDAC1 has been shown to be closely associated with the occurrence of tumors. We aimed to investigate the effects of siRNA-mediated HDAC1 knockdown on the biological behavior of esophageal carcinoma cell lines. MATERIAL AND METHODS HDAC1 expression in esophageal cancer cell lines TE-1, Eca109, and EC9706 was compared by Western blot analysis. These cells were transfected with siRNA-HDAC1 and cell proliferation was evaluated by MTT assay to select the optimum cell line for subsequent experiments. The effects of siRNA-HDAC1 on the migration and invasion of the selected cell line were assessed by transwell assay. The expression of cell cycle-related proteins cyclinD1, p21 and p27, and epithelial-mesenchymal transition (EMT)-related protein zonula occludens-1 (ZO-1), E-cadherin and vimentin was determined by Western blot analysis. RESULTS HDAC1 expression in TE-1, Eca109 and EC9706 cells was significantly higher compared with normal esophageal cell line HEEC (P<0.01). MTT assay, Western blot and RT-PCR analyses demonstrated that the inhibitory effects of siRNA on HDAC1 expression and cell viability in TE-1 cells were the highest among all cell lines, which was therefore used in subsequent experiments. After TE-1 cells were transfected with siRNA-HDAC1, their migration and invasion were significantly lower compared with the controls (P<0.01). CyclinD1 and vimentin expression was significantly lower compared with the controls (P<0.01), whereas the expression of p21, p27, ZO-1 and E-cadherin was significantly higher (P<0.01). CONCLUSIONS The siRNA-mediated HDAC1 knockdown significantly inhibited the proliferation, migration and invasion of TE-1 cells probably by regulating the expression of cell cycle- and EMT-related proteins.
منابع مشابه
Lentivirus-mediated Knockdown of HDAC1 Uncovers Its Role in Esophageal Cancer Metastasis and Chemosensitivity
Histone deacetylationase 1 (HDAC1) is ubiquitously expressed in various cell lines and tissues and play an important role of regulation gene expression. Overexpression of HDAC1 has been observed in various types of cancers, which indicated that it might be a target for cancer therapy. To test HDAC1 inhibition for cancer treatment, the gene expression of HDAC1 was knockdown mediated by a lentivi...
متن کاملStudy of the role of siRNA mediated promoter methylation in DNMT3B knockdown and alteration of promoter methylation of CDH1, GSTP1 genes in MDA-MB -453 cell line
Promoter methylation is one of the main epigenetic mechanisms that lead to the inactivation of tumor suppressor genes during carcinogenesis. Due to the reversible nature of DNA methylation, many studies have been performed to correct theses epigenetic defects by inhibiting DNA methyltransferases (DNMTs). In this case novel therapeutics especially siRNA oligonucleotides have been used to specifi...
متن کاملStudy of the role of siRNA mediated promoter methylation in DNMT3B knockdown and alteration of promoter methylation of CDH1, GSTP1 genes in MDA-MB -453 cell line
Promoter methylation is one of the main epigenetic mechanisms that lead to the inactivation of tumor suppressor genes during carcinogenesis. Due to the reversible nature of DNA methylation, many studies have been performed to correct theses epigenetic defects by inhibiting DNA methyltransferases (DNMTs). In this case novel therapeutics especially siRNA oligonucleotides have been used to specifi...
متن کاملHDAC inhibition activates the apoptosome via Apaf1 upregulation in hepatocellular carcinoma
BACKGROUND Histone deacetylation, a common hallmark in malignant tumors, strongly alters the transcription of genes involved in the control of proliferation, cell survival, differentiation and genetic stability. We have previously shown that HDAC1, HDAC2, and HDAC3 (HDAC1-3) genes encoding histone deacetylases 1-3 are upregulated in primary human hepatocellular carcinoma (HCC). The aim of this ...
متن کاملProduction of Cyclin D1 specific siRNAs by double strand processing for gene therapy of esophageal squamous cell carcinoma
Background: RNAi (RNA interference) is a new strategy in gene therapy and biotechnology which provides new promises in the treatment of different diseases such as cancer and viral diseases. CCND1 which is a key gene in cell cycle is amplified and over expressed in esophageal cancer. The objective of this study was production and siRNAs for CCND1, the key gene in cell cycle. Materials and Metho...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 22 شماره
صفحات -
تاریخ انتشار 2016