Basic Study
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World J Gastroenterol. Oct 28, 2023; 29(40): 5543-5556
Published online Oct 28, 2023. doi: 10.3748/wjg.v29.i40.5543
Roles of phosphatidylinositol-3-kinases signaling pathway in inflammation-related cancer: Impact of rs10889677 variant and buparlisib in colitis-associated cancer
Nurul Nadirah Razali, Raja Affendi Raja Ali, Khairul Najmi Muhammad Nawawi, Azyani Yahaya, Norshafila Diana Mohd Rathi, Norfilza Mohd Mokhtar
Nurul Nadirah Razali, Norshafila Diana Mohd Rathi, Norfilza Mohd Mokhtar, Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras 56000, Kuala Lumpur, Malaysia
Raja Affendi Raja Ali, School of Medical and Life Sciences, Sunway University, Sunway City 47500, Malaysia
Raja Affendi Raja Ali, Khairul Najmi Muhammad Nawawi, Norfilza Mohd Mokhtar, GUT Research Group, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras 56000, Kuala Lumpur, Malaysia
Raja Affendi Raja Ali, Khairul Najmi Muhammad Nawawi, Gastroenterology Unit, Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras 56000, Kuala Lumpur, Malaysia
Azyani Yahaya, Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras 56000, Kuala Lumpur, Malaysia
Author contributions: Mokhtar NM and Raja Ali RA contributed to the conceptualization; Mokhtar NM, Raja Ali RA, Muhammad Nawawi KN, and Razali NN contributed to the methodology and participant recruitments; Razali NN, and Mohd Rathi ND contributed to the animal handling; Razali NN, Yahaya A, and Mokhtar NM performed the validation; Razali NN, and Mokhtar NM contributed to the data analysis; Razali NN wrote the original draft preparation; Mokhtar NM, Raja Ali RA, and Muhammad Nawawi KN wrote the review and editing; Mokhtar NM, Raja Ali RA, and Muhammad Nawawi KN contributed to the supervision; All authors have read and agreed to the published version of the manuscript.
Supported by The Fundamental Research Grant Scheme, Ministry of Higher Education, Malaysia, No. FRGS/1/2018/SKK06/UKM/02/4.
Institutional review board statement: The human study has been approved under the Universiti Kebangsaan Malaysia Research Ethics Committee with a reference number: UKM/PPI/111/8/JEP-2019-572.
Institutional animal care and use committee statement: The animal study has been approved under the Animal Ethics Committee of Universiti Kebangsaan Malaysia with a reference number: PPUKM/2019/NORFILZA/25-SEPT./1035-SEPT.-2019-DEC.-2021 has approved the animal handling protocol.
Informed consent statement: Written informed consent was obtained from all the patients.
Conflict-of-interest statement: There is no conflict of interest.
Data sharing statement: Our raw data will be shared upon official request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Norfilza Mohd Mokhtar, PhD, Professor, Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras 56000, Kuala Lumpur, Malaysia. norfilza@ppukm.ukm.edu.my
Received: July 20, 2023
Peer-review started: July 20, 2023
First decision: August 25, 2023
Revised: September 5, 2023
Accepted: October 11, 2023
Article in press: October 11, 2023
Published online: October 28, 2023
Processing time: 99 Days and 6.5 Hours
Core Tip

Core Tip: The role of phosphatidylinositol-3-kinases (PI3K) in promoting cancer progression has been widely acknowledged due to its crucial involvement in regulating the survival, differentiation, and proliferation of cancer cells. Here, we investigate the role of PI3K signaling in colitis-associated cancer (CAC) pathogenesis by studying the regulation of potential variant in PI3K-related gene in the colorectal cancer cell line and the utilization of PI3K inhibitor, buparlisib, in the CAC-induced mice model. We suggested that rs10889677 variant plays a crucial role in initiating the PI3K signaling pathway, and buparlisib has the capability to inhibit PI3K-non-AKT activation in the pathophysiology of CAC.