MicroRNA-383-5p inhibits the progression of gastric carcinoma via targeting HDAC9 expression

MicroRNAs (miRNAs), as post-transcriptional regulators, have been reported to be involved in the initiation and progression of various types of cancer, including gastric cancer (GC). The present study aimed to investigate the role of miR-383-5p in gastric carcinogenesis. Cell viability was analyzed using CCK-8 kit. Annexin V-fluorescein isothiocyanate/propidium iodide double staining was used to evaluate cell apoptosis. The expression levels of miR-383-5p and histone deacetylase 9 (HDAC9) mRNA in GC tissues and cell lines were analyzed using RT-qPCR. The protein expression of HDAC9 was detected by western blotting. We found that HDAC9 was up-regulated and miR-383-5p was down-regulated in GC tissues and cell lines. High HDAC9 expression or low miR-383-5p expression was closely related to poor prognosis and metastasis in GC patients. HDAC9 knockout or miR-383-5p mimics led to growth inhibition and increased apoptosis in AGS and SGC-7901 cells. More importantly, we validated that miR-383-5p as a post-transcriptional regulator inhibited HDAC9 expression and was inversely correlated with HDAC9 expression in GC tissues. miR-383-5p had the opposite effects to HDAC9 in gastric carcinogenesis. miR-383-5p played an important role in gastric carcinogenesis, and it is one of the important mechanisms to regulate oncogenic HDAC9 in GC, which might be helpful in the development of novel therapeutic strategies for the treatment of GC.

Research progress on the role of histone deacetylase 9 in tumors / 中国肿瘤临床

Histone deacetylase 9 (HDAC9) belongs to the IIa subtype of HDACs. It is responsible for changing the structure of chromo-somes and regulating the transcription of genes by catalyzing the deacetylation of H3, H4, and non-histone proteins in vivo. Emerging studies have demonstrated that HDAC9 is closely related to tumors, but their expression and function in different tumors is not the same. This could ultimately lead to the opposite effect of promoting or suppressing tumorigenesis; unfortunately, the mechanisms are not clear. Recently, epigenetic treatment with HDAC deacetylases inhibitors (HDACIs) has become a hot topic and the development of selective HDACIs in combination with chemotherapy, radiotherapy, and immunotherapy has gained traction. However, studies target-ing HDAC9 are limited. This review summarizes the recent studies about HDAC9 in tumors.

Correlation between histone deacetylase 9 gene single nucleotide polymorphisms and ischemic stroke / 中国脑血管病杂志

Objective To investigate the correlation between histone deacetylase 9 gene ( HDAC9 ) single nucleotide polymorphisms and ischemic stroke ( IS) subtypes. Methods A total of 202 patients with IS were enrolled prospectively. According to the Trial of Org 10172 in Acute Stroke Treatment ( TOAST) classification,the patients with IS were divided into large artery atherosclerotic stroke group (LAA,n=149) and the small-artery occlusive stroke group (SAO,n=53). A total of 201 age- and sex-matched healthy subjects over the same period were enrolled as the control group. Polymerase chain reaction-ligase detection reaction ( PCR-LDR ) was used to perform genotyping for HDAC9 gene rs11984041 and rs2107595 loci in all subjects. The correlation between genotype and IS was analyzed with multivariate logistic regression analysis. Results ( 1 ) In all the subjects detected, the genotype detected from rs11984041 loci was type CC,and 3 genotypes including CC,CT,and TT were detected from rs2107595 loci. (2) There were significant differences in dominance model (CT+TT,CC) genotypes and allele frequencies among the LAA, SAO, and control group dominance model ( CT +TT, CC ) and (χ2 =8. 635,P=0. 013, χ2 =10. 309,P=0. 006);and there were no significant differences in dominance model (CT+TT,CC) and allele frequencies among the 3 groups (after adjustment all P>0. 017). Compared with the control group,there were significant differences in the CC,CT,and TT genotypes and allele frequencies in the LAA group (χ2 =7. 446;P=0. 006). In the dominance models (CT+TT),there was significant difference in genotype frequencies between the LAA group ( 65. 1%,97/149 ) and the control group (52. 2%,105/201) (χ2 =5. 800;P=0. 016). (3) Multivariate logistic regression analysis showed that in addition to gender,hypertension,smoking,and high level of low-density lipoprotein,the dominance model CT+TT genotype was associated with the LAA type IS ( CT+TT genotype:OR,1. 909,95% CI 1. 055-3. 454,P =0. 033). Conclusion In addition to the risk factors for cerebrovascular disease such as gender,hypertension,smoking,and high level of low-density lipoprotein,HDAC9 gene polymorphisms may be associated with the LAA type IS. rs2107595 locus CT + TT genotype may be an independent risk factor for LAA type IS.