RT Journal Article
SR Electronic
T1 Prediction of Angiopoietin-like Protein 4-related Signaling Pathways in Cholangiocarcinoma Cells
JF Cancer Genomics - Proteomics
JO Cancer Genomics Proteomics
FD International Institute of Anticancer Research
SP 490
OP 502
DO 10.21873/cgp.20335
VO 19
IS 4
A1 TIN MAY AUNG
A1 ATIT SILSIRIVANIT
A1 APINYA JUSAKUL
A1 WARAPORN CHAN-ON
A1 TANAKORN PROUNGVITAYA
A1 SITTIRUK ROYTRAKUL
A1 SIRIPORN PROUNGVITAYA
YR 2022
UL http://cgp.iiarjournals.org/content/19/4/490.abstract
AB 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 down-regulated. 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.