Histone deacetylase 3 (HDAC3) inhibits breast cancer cell pyroptosisby via regulating miR-625/ASF1B axis
10.3760/cma.j.cn.115807-20211127-00361
- VernacularTitle:组蛋白去乙酰化酶3通过调节miR-625/ASF1B轴抑制乳腺癌细胞焦亡
- Author:
Pingping SHANG
1
;
Yanming ZHANG
;
Xiangchen WANG
;
Licheng XU
Author Information
1. 烟台市烟台山医院检验科，烟台 264000
- Keywords:
Histone deacetylase 3 (HDAC3);
miR-625;
ASF1B;
Breast cancer;
Pyroptosis
- From:
Chinese Journal of Endocrine Surgery
2022;16(5):541-547
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effects of histone deacetylase 3 (HDAC3) on the pyroptosis of breast cancer (BC) cells via regulating miR-625/anti-silencing function 1B (ASF1B) and its mechanism.Methods:The expression level of HDAC3, miR-625 and ASF1B in BC tissue, adjacent normal tissue, BC cell lines (T47D, MCF7 and MDA-MB-231) and human normal breast epithelial cell MCF-10A was detected by qRT-PCR. The expression level of cell pyroptosis related protein NLRP3, Caspase-1 and GSDMD was detected by Western blot. The expression level of IL-18 and IL-1βwere detected by ELISA. ChIP experiment was used to determine the interaction between HDAC3 and miR-625. The dual luciferase reporter assay was used to verifiy the targeted regulation between miR-625 and ASF1B.Results:Compared with adjacent normal tissue and MCF-10A cells, the expression of HDAC3 and ASF1B was increased and the expression of miR-625 was decreased in BC tissue and cells (all P<0.05) . Compared with si-NC group, the protein expression level of NLRP3, Caspase-1 and GSDMD in si-HDAC3 group was increased, and the concentration of IL-18 and IL-1β in cell culture supernatant was increased (all P<0.05) . HDAC3 inhibited the expression of miR-625 by binding to the promoter region of miR-625 ( P<0.05) . Compared with si-HDAC3+miR-NC group, The expression of NLRP3, Caspase-1, GSDMD, IL-18 and IL-1β in si-HDAC3+miR-625 inhibitor group was decreased (all P<0.05) . ASF1B was confirmed as a target gene of miR-625, the level of pyroptosis related factors in si-HDAC3+pcDNA3.1-ASF1B group was significantly lower than that in si-HDAC3 + pcDNA3.1-NC group. Conclusion:HDAC3 up regulates the expression of ASF1B by inhibiting miR-625, and then inhibits BC cell pyroptosis.
