Objective

Our study aims to identify the impact of histone deacetylase 3 (HDAC3) and microRNA-376c-3p (miR-376c-3p) on gastric cancer (GC) by targeting wingless-type MMTV integration site family member 2b (WNT2b).

Methods

Levels of miR-376c-3p, HDAC3 and WNT2b were assessed. GC cells were treated with altered HDAC3 or miR-376c-3p to evaluate their biological functions, and rescue experiment was performed to assess the effect of WNT2b on GC cells. The tumor growth in vivo was observed.

Results

HDAC3 and WNT2b were up-regulated while miR-376c-3p was reduced in GC tissues and cell lines. The inhibited HDAC3 or elevated miR-376c-3p could restrain malignant behaviors of GC cells in vitro, and also suppress the xenograft growth. WNT2b silencing reduced the effect of miR-376c-3p inhibition while WNT2b overexpression mitigated that of miR-376c-3p promotion on GC cell growth.

Conclusion

Inhibiting HDAC3 promotes miR-376c-3p to suppress malignant phenotypes of GC cells via reducing WNT2b, thereby restricting GC development.

中文翻译：

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抑制的 HDAC3 通过减少 WNT2b 促进 microRNA-376c-3p 抑制胃癌细胞的恶性表型

客观的

我们的研究旨在通过靶向无翼型 MMTV 整合位点家族成员 2b (WNT2b) 来确定组蛋白去乙酰化酶 3 (HDAC3) 和 microRNA-376c-3p (miR-376c-3p) 对胃癌 (GC) 的影响。

方法

评估了 miR-376c-3p、HDAC3 和 WNT2b 的水平。GC细胞用改变的HDAC3或miR-376c-3p处理以评估其生物学功能，并进行拯救实验以评估WNT2b对GC细胞的影响。观察到体内肿瘤生长。

结果

HDAC3 和 WNT2b 上调，而 miR-376c-3p 在 GC 组织和细胞系中减少。抑制的HDAC3或升高的miR-376c-3p可以抑制GC细胞的体外恶性行为，也可以抑制异种移植物的生长。WNT2b 沉默降低了 miR-376c-3p 抑制的影响，而 WNT2b 过表达减轻了 miR-376c-3p 促进对 GC 细胞生长的影响。

结论

抑制 HDAC3 促进 miR-376c-3p通过减少 WNT2b抑制 GC 细胞的恶性表型，从而限制 GC 发展。