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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. May 15, 2020; 12(5): 514-525
Published online May 15, 2020. doi: 10.4251/wjgo.v12.i5.514
Free fatty acids receptors 2 and 3 control cell proliferation by regulating cellular glucose uptake
Saeed Al Mahri, Amal Al Ghamdi, Maaged Akiel, Monira Al Aujan, Sameer Mohammad, Mohammad Azhar Aziz
Saeed Al Mahri, Amal Al Ghamdi, Maaged Akiel, Monira Al Aujan, Sameer Mohammad, Mohammad Azhar Aziz, King Abdullah International Medical Research Center, Riyadh 11426, Saudi Arabia
Saeed Al Mahri, Amal Al Ghamdi, Maaged Akiel, Monira Al Aujan, Sameer Mohammad, Mohammad Azhar Aziz, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11426, Saudi Arabia
Saeed Al Mahri, Amal Al Ghamdi, Monira Al Aujan, Sameer Mohammad, Mohammad Azhar Aziz, Ministry of the National Guard - Health Affairs, Riyadh 11426, Saudi Arabia
Saeed Al Mahri, Sameer Mohammad, Department of Experimental Medicine, King Abdullah International Medical Research Center, Riyadh 11426, Saudi Arabia
Amal Al Ghamdi, Mohammad Azhar Aziz, Colorectal Cancer Research Program, King Abdullah International Medical Research Center, Riyadh 11426, Saudi Arabia
Maaged Akiel, Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11426, Saudi Arabia
Maaged Akiel, Monira Al Aujan, Department of Medical Genomics, King Abdullah International Medical Research Center, Riyadh 11426, Saudi Arabia
Maaged Akiel, Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23284, United States
Author contributions: Mohammad S and Aziz MA conceived the idea and designed research; Al Mahri S and Akiel M generated knockdown cell lines; Al Mahri S and Al Ghamdi A performed qRT-PCR assays; Al Mahri S and Mohammad S performed glucose uptake, cAMP signalling and immunofluorescence studies; Al Ghamdi A performed western blots and cell proliferation assay; Akiel M designed primers; Al Aujan M Assisted in maintaining knockdown cells; Aziz MA, Al Mahri S, Akiel M and Mohammad S analyzed data; Aziz MA, Akiel M and Mohammad S prepared final figures, wrote and edited the paper; Aziz MA carried out microarray and qRT-PCR analyses; All authors reviewed and endorsed all contents of the manuscript.
Institutional review board statement: This study was approved by Institutional Research Board of King Abdullah International Medical Research Center through protocol number RC15/153.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: This patient microarray dataset is available on Gene Expression Omnibus, National Center for Biotechnology Information, National Institute of Health, United States (Accession: GSE 50421).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Mohammad Azhar Aziz, BSc, MSc, PhD, Research Scientist, Colorectal Cancer Research Program, King Abdullah International Medical Research Center, P.O. Box 3660, Riyadh 11426, Saudi Arabia. azizmo@ngha.med.sa
Received: December 17, 2019
Peer-review started: December 17, 2019
First decision: February 20, 2020
Revised: March 18, 2020
Accepted: March 28, 2020
Article in press: March 28, 2020
Published online: May 15, 2020
ARTICLE HIGHLIGHTS
Research background
Colorectal cancer (CRC) has been linked with free fatty acid receptors (FFARs). However, the mechanism of action of FFARs in CRC needs to be better studied.
Research motivation
To generate evidence that can better explain the role of diet in CRC and its association with gut microbiome.
Research objectives
To understand how FFAR2 and FFAR3 contribute to CRC cell growth and metabolism.
Research methods
Cell culture, RNA interference (RNAi), Transfection, quantitative real time PCR, Western blot, Glucose uptake assay, cAMP assay, real time cell proliferation assay, Immunofluorescence, statistical and computational analyses.
Research results
FFAR2 is downregulated in CRC patient samples. CRC cells with reduced levels of FFAR2 and FFAR3 genes expression show increased rate of proliferation. Increased levels of glucose transporter and subsequent increase in glucose uptake is observed alongside increased cAMP levels in cells with reduced expression of FFAR2 and FFAR3.
Research conclusions
Short chain FFARs FFAR2 and FFAR3 may contribute in increased cell proliferation by increased glucose uptake.
Research perspectives
Processing of food by gut microbiota could be associated with initiation, progression and severity of CRC. Modifying dietary profiles for high-risk individuals may be a preventive measure for CRC.
