真核翻译起始因子3B（EIF3B）促进胰腺癌的癌症进展。

EIF3B promotes cancer progression in pancreatic cancer.

作者信息

Zhu Hanzhang, Shan Yuqiang, Ge Ke, Lu Jun, Kong Wencheng, Jia Changku

机构信息

Department of Hepatopancreatobiliary Surgery, Hangzhou First People's Hospital, The Affiliated Hospital of Medical School of Zhejiang University, Hangzhou, China.

Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou, China.

出版信息

Scand J Gastroenterol. 2021 Mar;56(3):281-288. doi: 10.1080/00365521.2020.1868566. Epub 2021 Jan 18.

DOI:10.1080/00365521.2020.1868566

PMID:33459066

Abstract

BACKGROUND

This study aimed to analyze the relative expression of Eukaryotic Translation Initiation Factor 3 Subunit B (EIF3B) in pancreatic cancer and elucidate its contribution to this disease.

METHODS

Relative expression of EIF3B in pancreatic cancer was analyzed by immunohistochemistry. Cell viability was determined by the MTT assay and cell proliferation was measured by direct cell counting. Cell apoptosis was detected by Annexin V staining followed by flow cytometry analysis, and cell cycle was analyzed by PI staining. The differential expression gene analysis was performed by microarray. Tumor progression in response to EIF3B deficiency was investigated using the xenograft tumor model.

RESULTS

We found aberrantly high expression of EIF3B in pancreatic cancer, which associated with unfavorable prognosis. Knockdown of EIF3B greatly compromised cell viability and proliferation in both SW1990 and PANC-1 cells. Furthermore, EIF3B deficiency induced cell cycle arrest and spontaneous apoptosis. tumor progression was significantly suppressed by EIF3B silencing in the xenograft mouse model. Mechanistically, we characterized down-regulation of CDH1 and IRS1 and up-regulation of DDIT3, PTEN and CDKN1B, in response to EIF3B knockdown, which might mediate the oncogenic effect of EIF3B in pancreatic cancer.

CONCLUSIONS

Our data uncovered the oncogenic role of EIF3B in pancreatic cancer.

摘要

背景

本研究旨在分析真核生物翻译起始因子3亚基B（EIF3B）在胰腺癌中的相对表达，并阐明其对该疾病的作用。

方法

采用免疫组织化学法分析EIF3B在胰腺癌中的相对表达。通过MTT法测定细胞活力，通过直接细胞计数测量细胞增殖。采用膜联蛋白V染色后进行流式细胞术分析检测细胞凋亡，通过PI染色分析细胞周期。利用基因芯片进行差异表达基因分析。使用异种移植肿瘤模型研究EIF3B缺乏对肿瘤进展的影响。

结果

我们发现EIF3B在胰腺癌中异常高表达，这与不良预后相关。在SW1990和PANC - 1细胞中，敲低EIF3B显著损害细胞活力和增殖。此外，EIF3B缺乏诱导细胞周期停滞和自发凋亡。在异种移植小鼠模型中，EIF3B沉默显著抑制肿瘤进展。机制上，我们发现响应EIF3B敲低，CDH1和IRS1表达下调，DDIT3、PTEN和CDKN1B表达上调，这可能介导了EIF3B在胰腺癌中的致癌作用。