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

Doungdean Tummanatsakun,Sittiruk Roytrakul,Siriporn Proungvitaya,Tanakorn Proungvitaya

doi:10.3390/molecules26092587

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.

Highlights

Cholangiocarcinoma (CCA) is a bile duct cancer originating from biliary epithelial cells [1]
ETxopraensasiloynzeofthAePsEiXgn1ailninCgelpl aLtihnwesay of apyrimidinic endodeoxyribonuclease 1 (APEX1) in the metastasis of CCA, we examined the ATPoEaXn1aelyxzperetshseiosniginnatlhinrgeepCatChAwacyelol fliAnePsE, XK1KiUn-t2h1e3Am,eKtaKstUa-s2is13oBf,CaCnAd,KwKeUe-x1a0m0,iannedd athneimAPmEoXr1taelixzperdescshioonlainngtihorceyeteCMCAMcNelKl 1li,nuessi,nKgKwUe-s2t1e3rAn,bKloKtUa-n2a1l3yBsi,sa.nTdhKe KAUPE-1X010,eaxnpdreasnsimionmoofrttahliezethdrecheoClaCnAgicoeclyltleinMesMwNaKs1h,iugshienrgtwhaensttehrnatbolof tMaMnaNlyKsi1s.(TFihgeuAreP1EAX,1Be),xwpriethsstiohne hoifgthheesttherxeeprCeCssAiocnelilnliKneKsUw-2a1s3hAighanerdththaen ltohwateostf MinMKNKKU1-1(0F0ig. uTrheu1sA,tBh)o,swe ittwh othceehlliglihneesst wexeprreeusssieodnaisnrKepKrUes-2e1n3taAtiavnedcethlles floowr geesnt einsKileKnUci-n1g00e.xTpheurism, tehnotsse. two cell lines were used as representative cells for gene silencing experiments
The results demonstrated that APEX1 RNA was significantly over-expressed in CCA compared with normal control tissue samples (Figure 6A)

Summary

Introduction

Cholangiocarcinoma (CCA) is a bile duct cancer originating from biliary epithelial cells [1]. In northeastern Thailand, a strong association was observed between CCA and age, Opisthorchis viverrini infection, the custom of eating raw cyprinoid fish contaminated with O. viverrini larvae, family history of cancer, and liquor consumption [3]. Surgical resection is the only possible curative treatment for CCA patients [4]. Useful biomarkers are necessary, for early diagnosis, and for predicting the prognosis of CCA patients [5]. Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) have been routinely used as biomarkers for the diagnosis/prognosis of CCA, the sensitivity and specificity of these markers could be improved [5,6,7]

Methods

Results

Discussion

Conclusion