Tin May Aung1, Atit Silsirivanit2,3, Apinya Jusakul1,3, Waraporn Chan-On4, Tanakorn Proungvitaya1, Sittiruk Roytrakul5, Siriporn Proungvitaya6,3. 1. Centre of Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand. 2. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. 3. Cholangiocarcinoma Research Institute, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. 4. Center for Research and Innovation, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, Thailand. 5. Functional Ingredients and Food Innovation Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand. 6. Centre of Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand; sirpat@kku.ac.th.
Abstract
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.
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.
Authors: Masanobu Maruyama; Naoya Kobayashi; Karen A Westerman; Masakiyo Sakaguchi; Jean E Allain; Toshinori Totsugawa; Teru Okitsu; Takuya Fukazawa; Anne Weber; Donna B Stolz; Philippe Leboulch; Noriaki Tanaka Journal: Transplantation Date: 2004-02-15 Impact factor: 4.939
Authors: Joanna C Chan; Katherine M Hannan; Kim Riddell; Pui Yee Ng; Abigail Peck; Rachel S Lee; Sandy Hung; Megan V Astle; Megan Bywater; Meaghan Wall; Gretchen Poortinga; Katarzyna Jastrzebski; Karen E Sheppard; Brian A Hemmings; Michael N Hall; Ricky W Johnstone; Grant A McArthur; Ross D Hannan; Richard B Pearson Journal: Sci Signal Date: 2011-08-30 Impact factor: 8.192
Authors: Tin May Aung; Mang Ngaih Ciin; Atit Silsirivanit; Apinya Jusakul; Worachart Lert-Itthiporn; Tanakorn Proungvitaya; Sittiruk Roytrakul; Siriporn Proungvitaya Journal: Front Public Health Date: 2022-03-22