Centre of Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Cancer Genomics Proteomics. 2022 Jul-Aug;19(4):490-502. doi: 10.21873/cgp.20335.
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.
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.
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).
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.
背景/目的：血管生成素样蛋白 4（ANGPTL4）是一种多功能信号蛋白，涉及碳水化合物代谢、炎症、癌症生长和进展、失巢凋亡抵抗、血管生成和转移。然而，胆管癌（CCA）中 ANGPTL4 的信号通路尚不清楚。本研究旨在探讨与 CCA 生物学相关的 ANGPTL4 相关信号蛋白和途径。
用小干扰 RNA（siRNA）沉默 CCA 细胞中的 ANGPTL4，用对照物和 ANGPTL4 相关信号蛋白进行质谱分析、生物信息学工具和分子对接研究。
在 321 个差异表达蛋白中，有 151 个下调。其中，生物信息学分析表明，ANGPTL4 通过 AKT 丝氨酸/苏氨酸激酶 1（AKT1）、雷帕霉素靶蛋白激酶（MTOR）和核糖体蛋白 L5（RPL5）与 DNA 依赖性蛋白激酶催化亚基（PRKDC）和 60S 核糖体蛋白 L21（RPL21）相互作用。在线数据库分析显示，ANGPTL4 相关信号蛋白的 mRNA 和蛋白表达水平在 CCA 中明显高于正常组织。此外，高 mRNA 表达水平与高肿瘤分级（p<0.0001）和淋巴结转移（p<0.0001）相关。
CCA 进展中 ANGPTL4 的信号通路可能受 PRKDC 和 RPL21 调节。此外，ANGPTL4 相关信号蛋白的高表达有可能用于临床预后。
