Bioinformatic Prediction of Novel Signaling Pathways of Apoptosis-inducing Factor, Mitochondrion-associated 3 (AIFM3) and Their Roles in Metastasis of Cholangiocarcinoma Cells

Chua‐On, Daraporn; Proungvitaya, Tanakorn; Techasen, Anchalee; Limpaiboon, Temduang; Roytrakul, Sittiruk; Tummanatsakun, Doungdean; Araki, Nobuhito; Proungvitaya, Siriporn

doi:10.21873/cgp.20302

Cited by 3 publications

(3 citation statements)

References 35 publications

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“…The three human CCA cell lines, KKU-M055 (JCRB1551), KKU-100 (JCRB1568) [11], and KKU-M213A, which was renamed from KKU-213 (JCRB1557) [12], and an immortalized cholangiocyte cell line, MMNK1 (JCRB1554) [13] were obtained from the Japanese Collection of Research Bioresources Cell Bank (Tokyo, Japan) and were kindly provided by CARI, KKU. The cell lines were cultured and subcultured as described previously [14]. All cell lines in this study were confirmed mycoplasma-free by specific PCR.…”

Section: Cca Cell Linesmentioning

confidence: 99%

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

Truong

Wongwattanakul

Proungvitaya

et al. 2022

JCM

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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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Section: Cca Cell Linesmentioning

confidence: 99%

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

Truong

Wongwattanakul

Proungvitaya

et al. 2022

JCM

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“…San et al demonstrated that knockdown of ANGPTL4 reduced the death of CCA cells (18). Proteomics approaches have been applied for determining cellular protein-protein interactions, signaling pathways and functions of proteins in cancer research (37)(38)(39). To our knowledge, this study is the first proteomic analysis to identify ANGPTL4-associated downstream proteins and signaling pathways in CCA cells.…”

Section: Figure 4 Correlation Of Gene-expression Levels Between Angio...mentioning

confidence: 87%

Prediction of Angiopoietin-like Protein 4-related Signaling Pathways in Cholangiocarcinoma Cells

Aung

Silsirivanit

Jusakul

et al. 2022

Cancer Genomics Proteomics

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Background/Aim: Angiopoietin-like protein 4 (ANGPTL4) is a multifunctional signaling protein implicated in carbohydrate metabolism, inflammation, cancer growth and progression, anoikis resistance, angiogenesis, and metastasis. However, signaling pathways of ANGPTL4 in cholangiocarcinoma (CCA) remain unknown. The aim of this study was to explore ANGPTL4-related signaling proteins and pathways associated with CCA biology. Materials and Methods: ANGPTL4 of CCA cells was silenced by small interfering RNA (siRNA) with scramble control and ANGPTL4-related signaling proteins were investigated using mass spectrometry, bioinformatics tools and molecular docking. Results: Among the 321 differentially expressed proteins, 151 were downregulated. Among them, bioinformatic analyses revealed that ANGPTL4 interacts with DNA-dependent protein kinase catalytic subunit (PRKDC) and 60S ribosomal protein L21 (RPL21) via AKT serine/threonine kinase 1 (AKT1), mechanistic target of rapamycin kinase (MTOR) and ribosomal protein L5 (RPL5). Online database analysis showed that mRNA and protein expression levels of ANGPTL4-related signaling proteins were significantly higher in CCA than in normal tissues. Moreover, a high mRNA expression level was associated with high tumor grade (p<0.0001) and lymph node metastasis (p<0.0001). Conclusion: The signaling pathway of ANGPTL4 in CCA progression might be regulated by PRKDC and RPL21. Furthermore, high expression of ANGPTL4-related signaling proteins has potential to be used in clinical prognosis.Cholangiocarcinoma (CCA) is a type of highly aggressive cancer that can develop anywhere in the biliary tree or within the liver parenchyma (1). It is a rare cancer worldwide, but it is highly prevalent in Thailand, with the highest prevalence of 85/100,000 population being recorded in northeast Thailand and in association with the high prevalence of infection with the oncogenic liver fluke (Opisthorchis viverrini) (2-4). Although complete surgical resection is the only curative treatment for CCA, the postoperative 5-year survival rate of patients remains low (11.2%) due to late presentation of clinical symptoms (5, 6). Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) are currently used tumor markers for clinical diagnosis/prognosis of CCA. However, elevation of these markers has also been found in benign biliary diseases, pancreatic cancer, and colorectal cancer, amongst others (7-9). Hence, developing reliable biomarkers and exploring the mechanisms underlying CCA progression are essential to improve the outcomes of patients with CCA.Angiopoietin-like protein 4 (ANGPTL4) is a secreted protein with a highly hydrophobic signal peptide and has an N-terminal coiled-coil domain and a C-terminal fibrinogen-like fragment (10). It has a variety of biological roles in both normal and 490

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“…AIFM3 shares 35% of its sequence with the apoptosis-inducing factor (AIF). AIFM3 is also capable of inducing apoptosis (10).…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of Apoptotic Genes in Polycystic Ovarian Syndrome Patients Undergoing In-vitro Fertilization

Sayed

Radwan

Reda

et al. 2023

ERU Research Journal

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Polycystic Ovary Syndrome (PCOS) is a common endocrine-reproductive disease in females. Cell apoptosis plays an important role in follicular development, mainly in egg production, oocyte degeneration, follicle selection, or even follicle atresia. It also serves an important part in the embryo's early growth and differentiation into a complete organism. PCOS is a condition that is known to be caused by alterations in cell development and cell death factors, as well as oxidative stress, resulting in follicular interruptions and immature follicles.Apoptosis is a natural homeostatic process that helps the tissue remove the growing number of unwanted cells that are harmed during development, growth, or senescence. Caspases, an inhibitor of apoptosis proteins, the B cell lymphoma (Bcl)-2 gene family, the tumour necrosis factor (TNF) receptor superfamily, and the p53 gene are all participating and/or cooperating in the apoptosis pathway. Microarray data analysis of PCOS databases obtained from GEO datasets was performed to identify significant dysregulated apoptotic genes in PCOS oocytes compared to controls.

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Bioinformatic Prediction of Novel Signaling Pathways of Apoptosis-inducing Factor, Mitochondrion-associated 3 (AIFM3) and Their Roles in Metastasis of Cholangiocarcinoma Cells

Cited by 3 publications

References 35 publications

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

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

Prediction of Angiopoietin-like Protein 4-related Signaling Pathways in Cholangiocarcinoma Cells

Dysregulation of Apoptotic Genes in Polycystic Ovarian Syndrome Patients Undergoing In-vitro Fertilization

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