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嘌呤/嘧啶内切核酸酶 1（APEX1）信号通路的生物信息学预测及其在胆管癌细胞中的作用。

Bioinformatic Prediction of Signaling Pathways for Apurinic/Apyrimidinic Endodeoxyribonuclease 1 (APEX1) and Its Role in Cholangiocarcinoma Cells.

机构信息

Centre of Research and Development of Medical Diagnostic Laboratories (CMDL), Faculty of Associated Medical Sciences, KhonKaen University, KhonKaen 40002, Thailand.

National Center for Genetic Engineering and Biotechnology (BIOTEC), Functional Ingredients and Food Innovation Research Group, National Science and Technology Development Agency (NSTDA), Pathumthani 12120, Thailand.

出版信息

Molecules. 2021 Apr 29;26(9):2587. doi: 10.3390/molecules26092587.

DOI:10.3390/molecules26092587
PMID:33946672
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8125001/
Abstract

Apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) is involved in the DNA damage repair pathways and associates with the metastasis of several human cancers. However, the signaling pathway of APEX1 in cholangiocarcinoma (CCA) has never been reported. In this study, to predict the signaling pathways of APEX1 and related proteins and their functions, the effects of APEX1 gene silencing on APEX1 and related protein expression in CCA cell lines were investigated using mass spectrometry and bioinformatics tools. Bioinformatic analyses predicted that APEX1 might interact with cell division cycle 42 (CDC42) and son of sevenless homolog 1 (SOS1), which are involved in tumor metastasis. RNA and protein expression levels of APEX1 and its related proteins, retrieved from the Gene Expression Profiling Interactive Analysis (GEPIA) and the Human Protein Atlas databases, revealed that their expressions were higher in CCA than in the normal group. Moreover, higher levels of APEX1 expression and its related proteins were correlated with shorter survival time. In conclusion, the signaling pathway of APEX1 in metastasis might be mediated via CDC42 and SOS1. Furthermore, expression of APEX1 and related proteins is able to predict poor survival of CCA patients.

摘要

脱嘌呤/脱嘧啶核酸内切酶 1（APEX1）参与 DNA 损伤修复途径，并与几种人类癌症的转移有关。然而，APEX1 在胆管癌（CCA）中的信号通路从未被报道过。在这项研究中，为了预测 APEX1 和相关蛋白的信号通路及其功能，使用质谱和生物信息学工具研究了 APEX1 基因沉默对 CCA 细胞系中 APEX1 和相关蛋白表达的影响。生物信息学分析预测 APEX1 可能与细胞分裂周期 42（CDC42）和 Src 同源物 7 缺失 1（SOS1）相互作用，这两者都参与肿瘤转移。从基因表达谱交互分析（GEPIA）和人类蛋白质图谱数据库中检索到的 APEX1 及其相关蛋白的 RNA 和蛋白表达水平表明，它们在 CCA 中的表达高于正常组。此外，APEX1 表达及其相关蛋白水平升高与生存时间缩短相关。总之，APEX1 在转移中的信号通路可能通过 CDC42 和 SOS1 介导。此外，APEX1 和相关蛋白的表达能够预测 CCA 患者的不良预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fed/8125001/360eabf66c13/molecules-26-02587-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fed/8125001/0f2db57d6370/molecules-26-02587-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fed/8125001/8e312b98b384/molecules-26-02587-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fed/8125001/fba688b3ab17/molecules-26-02587-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fed/8125001/3ebde17dfdff/molecules-26-02587-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fed/8125001/6ce60c85be51/molecules-26-02587-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fed/8125001/c1911c9aad43/molecules-26-02587-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fed/8125001/360eabf66c13/molecules-26-02587-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fed/8125001/0f2db57d6370/molecules-26-02587-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fed/8125001/8e312b98b384/molecules-26-02587-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fed/8125001/fba688b3ab17/molecules-26-02587-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fed/8125001/3ebde17dfdff/molecules-26-02587-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fed/8125001/6ce60c85be51/molecules-26-02587-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fed/8125001/c1911c9aad43/molecules-26-02587-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fed/8125001/360eabf66c13/molecules-26-02587-g007.jpg

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