Prediction of CIAPIN1 (Cytokine-Induced Apoptosis Inhibitor 1) Signaling Pathway and Its Role in Cholangiocarcinoma Metastasis

Cholangiocarcinoma (CCA), a malignancy of the biliary epithelium, can arise at any point in the biliary system. We previously reported that CIAPIN1 is detectable in the sera and that its overexpression was associated with poor prognosis and metastasis of CCA patients. In this study, we investigated...

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Main Authors: Son Dinh An Truong, Molin Wongwattanakul, Tanakorn Proungvitaya, Temduang Limpaiboon, Sittiruk Roytrakul, Daraporn Chua-on, Doungdean Tummanatsakun, Siriporn Proungvitaya
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:Journal of Clinical Medicine
Subjects:
Online Access:https://www.mdpi.com/2077-0383/11/13/3826
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author Son Dinh An Truong
Molin Wongwattanakul
Tanakorn Proungvitaya
Temduang Limpaiboon
Sittiruk Roytrakul
Daraporn Chua-on
Doungdean Tummanatsakun
Siriporn Proungvitaya
author_facet Son Dinh An Truong
Molin Wongwattanakul
Tanakorn Proungvitaya
Temduang Limpaiboon
Sittiruk Roytrakul
Daraporn Chua-on
Doungdean Tummanatsakun
Siriporn Proungvitaya
author_sort Son Dinh An Truong
collection DOAJ
description Cholangiocarcinoma (CCA), a malignancy of the biliary epithelium, can arise at any point in the biliary system. We previously reported that CIAPIN1 is detectable in the sera and that its overexpression was associated with poor prognosis and metastasis of CCA patients. In this study, we investigated further its expression in CCA tissues, biological functions, and related signaling pathways in CCA cells. First, we examined CIAPIN1 expression in CCA tissues of 39 CCA patients using immunohistochemistry (IHC). Then, CIAPIN1-related proteins expressed in CCA cells were identified using RNA interference (siRNA) and liquid chromatography–mass spectrometry (LC–MS/MS). To predict the functions and signaling pathways of CIAPIN1 in CCA cells, the identified proteins were analyzed using bioinformatics tools. Then, to validate the biological functions of CIAPIN1 in the CCA cell line, transwell migration/invasion assays were used. CIAPIN1 was overexpressed in CCA tissues compared with adjacent noncancerous tissues. Its overexpression was correlated with lymph node metastasis. Bioinformatic analyses predicted that CIAPIN1 is connected to the TGF-β/SMADs signaling pathway via nitric oxide synthase 1 (NOS1) and is involved in the metastasis of CCA cells. In fact, cell migration and invasion activities of the KKU-100 CCA cell line were significantly suppressed by CIAPIN1 gene silencing. Our results unravel its novel function and potential signaling pathway in metastasis of CCA cells. CIAPIN1 can be a poor prognostic factor and can be a promising target molecule for CCA chemotherapy.
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spelling doaj.art-a25b4b0a5fc04b09b947797adbb9afd22023-12-03T14:08:40ZengMDPI AGJournal of Clinical Medicine2077-03832022-07-011113382610.3390/jcm11133826Prediction of CIAPIN1 (Cytokine-Induced Apoptosis Inhibitor 1) Signaling Pathway and Its Role in Cholangiocarcinoma MetastasisSon Dinh An Truong0Molin Wongwattanakul1Tanakorn Proungvitaya2Temduang Limpaiboon3Sittiruk Roytrakul4Daraporn Chua-on5Doungdean Tummanatsakun6Siriporn Proungvitaya7Centre of Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, ThailandCentre of Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, ThailandCentre of Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, ThailandCentre of Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, ThailandNational Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani 12120, ThailandCentre of Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, ThailandCentre of Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, ThailandCentre of Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, ThailandCholangiocarcinoma (CCA), a malignancy of the biliary epithelium, can arise at any point in the biliary system. We previously reported that CIAPIN1 is detectable in the sera and that its overexpression was associated with poor prognosis and metastasis of CCA patients. In this study, we investigated further its expression in CCA tissues, biological functions, and related signaling pathways in CCA cells. First, we examined CIAPIN1 expression in CCA tissues of 39 CCA patients using immunohistochemistry (IHC). Then, CIAPIN1-related proteins expressed in CCA cells were identified using RNA interference (siRNA) and liquid chromatography–mass spectrometry (LC–MS/MS). To predict the functions and signaling pathways of CIAPIN1 in CCA cells, the identified proteins were analyzed using bioinformatics tools. Then, to validate the biological functions of CIAPIN1 in the CCA cell line, transwell migration/invasion assays were used. CIAPIN1 was overexpressed in CCA tissues compared with adjacent noncancerous tissues. Its overexpression was correlated with lymph node metastasis. Bioinformatic analyses predicted that CIAPIN1 is connected to the TGF-β/SMADs signaling pathway via nitric oxide synthase 1 (NOS1) and is involved in the metastasis of CCA cells. In fact, cell migration and invasion activities of the KKU-100 CCA cell line were significantly suppressed by CIAPIN1 gene silencing. Our results unravel its novel function and potential signaling pathway in metastasis of CCA cells. CIAPIN1 can be a poor prognostic factor and can be a promising target molecule for CCA chemotherapy.https://www.mdpi.com/2077-0383/11/13/3826cholangiocarcinomaCIAPIN1prognosissiRNAproteomicsmetastasis
spellingShingle Son Dinh An Truong
Molin Wongwattanakul
Tanakorn Proungvitaya
Temduang Limpaiboon
Sittiruk Roytrakul
Daraporn Chua-on
Doungdean Tummanatsakun
Siriporn Proungvitaya
Prediction of CIAPIN1 (Cytokine-Induced Apoptosis Inhibitor 1) Signaling Pathway and Its Role in Cholangiocarcinoma Metastasis
Journal of Clinical Medicine
cholangiocarcinoma
CIAPIN1
prognosis
siRNA
proteomics
metastasis
title Prediction of CIAPIN1 (Cytokine-Induced Apoptosis Inhibitor 1) Signaling Pathway and Its Role in Cholangiocarcinoma Metastasis
title_full Prediction of CIAPIN1 (Cytokine-Induced Apoptosis Inhibitor 1) Signaling Pathway and Its Role in Cholangiocarcinoma Metastasis
title_fullStr Prediction of CIAPIN1 (Cytokine-Induced Apoptosis Inhibitor 1) Signaling Pathway and Its Role in Cholangiocarcinoma Metastasis
title_full_unstemmed Prediction of CIAPIN1 (Cytokine-Induced Apoptosis Inhibitor 1) Signaling Pathway and Its Role in Cholangiocarcinoma Metastasis
title_short Prediction of CIAPIN1 (Cytokine-Induced Apoptosis Inhibitor 1) Signaling Pathway and Its Role in Cholangiocarcinoma Metastasis
title_sort prediction of ciapin1 cytokine induced apoptosis inhibitor 1 signaling pathway and its role in cholangiocarcinoma metastasis
topic cholangiocarcinoma
CIAPIN1
prognosis
siRNA
proteomics
metastasis
url https://www.mdpi.com/2077-0383/11/13/3826
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