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PRDM5 抑制食管鳞癌细胞并调节 14-3-3zeta/Akt 信号通路。

PRDM5 suppresses oesophageal squamous carcinoma cells and modulates 14-3-3zeta/Akt signalling pathway.

机构信息

Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of General Thoracic Surgery, Hami Central Hospital, Hami, China.

出版信息

Clin Exp Pharmacol Physiol. 2022 Mar;49(3):370-379. doi: 10.1111/1440-1681.13612. Epub 2021 Nov 23.

Abstract

Dysregulation of PR (PRDI-BF1 and RIZ) domain protein 5 (PRDM5) expression has been shown to be associated with the progression of many malignancies. Nevertheless, the role and underlying mechanism of PRDM5 in oesophageal squamous cell carcinoma (ESCC) remain elusive. qRT-PCR was performed to analyze PRDM5 mRNA expression, and western blot was used to determine protein expression of PRDM5, MMP-2, MMP-9, 14-3-3zeta, pan-Akt and phosphorylated Akt expression. CCK-8 staining was employed to evaluate cell proliferation, while wound scratch assay and Transwell assay were carried out to detect cell migration. A tumour xenograft model of ESCC was also established to validate the effect of PRDM5. PRDM5 expression was downregulated in ESCC tissues and positively correlated with the overall survival of ESCC patients. Silencing PRDM5 expression promoted cell proliferation in ESCC cells, while overexpressing PRDM5 inhibited cell proliferation. Moreover, the migratory abilities of ESCC cells were promoted by PRDM5 knockdown but were attenuated by PRDM5 overexpression. Importantly, 14-3-3zeta expression, along with the phosphorylation of Akt, was suppressed by PRDM5 in ESCC cells. In the established tumour xenograft model, PRDM5 regulated ESCC tumour growth as well as the expression of 14-3-3zeta and phosphorylation of Akt protein. In conclusion, PRDM5 suppresses ESCC cell proliferation and migration and negatively regulates 14-3-3zeta/Akt signalling pathway in vitro and in vivo.

摘要

PR (PRDI-BF1 和 RIZ) 结构域蛋白 5 (PRDM5) 表达失调与许多恶性肿瘤的进展有关。然而,PRDM5 在食管鳞状细胞癌 (ESCC) 中的作用和潜在机制仍不清楚。通过 qRT-PCR 分析 PRDM5 mRNA 表达,通过 Western blot 测定 PRDM5、MMP-2、MMP-9、14-3-3zeta、pan-Akt 和磷酸化 Akt 的蛋白表达。CCK-8 染色用于评估细胞增殖,而划痕实验和 Transwell 实验用于检测细胞迁移。还建立了 ESCC 的肿瘤异种移植模型以验证 PRDM5 的作用。PRDM5 在 ESCC 组织中表达下调,与 ESCC 患者的总生存率呈正相关。沉默 PRDM5 表达促进 ESCC 细胞增殖,而过表达 PRDM5 抑制细胞增殖。此外,PRDM5 敲低促进 ESCC 细胞的迁移能力,而过表达 PRDM5 则减弱了这种能力。重要的是,在 ESCC 细胞中,14-3-3zeta 的表达以及 Akt 的磷酸化被 PRDM5 抑制。在建立的肿瘤异种移植模型中,PRDM5 调节 ESCC 肿瘤生长以及 14-3-3zeta 和磷酸化 Akt 蛋白的表达。总之,PRDM5 抑制 ESCC 细胞增殖和迁移,并在体外和体内负调控 14-3-3zeta/Akt 信号通路。

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