Page 99 - TD-3-4

Tumor Discovery

ORIGINAL RESEARCH ARTICLE
Bioinformatics approach to identifying potential

cancer-associated mutations in CCL2

Shah Kamal 1† , Najeeb Ullah 1† , Amanullah Amanullah 1 ,
1
Mariam Ahmed Mujtaba 2 , Kashif Ali Khan 3 , Cheng Deng * ,
Shanshan Lai * , and Mohammad Amjad Kamal 4,5,6,7,8 *
1
1 Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing
Normal University, Nanjing, China
2 Department of Biotechnology, Women University Mardan, East Canal Road Mardan, 23200, Pakistan
3 Department of Pharmacy, Shaheed Benazir Bhutto University Sheringal, Dir Upper, Pakistan
4 Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network,
West China School of Nursing, West China Hospital, Sichuan University, Chengdu, China
5 King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
6 Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University,
Dhaka, Bangladesh

Abstract
† These authors contributed equally
to this work. Chemokine C-C motif ligand 2 (CCL2), also known as monocyte chemoattractant
*Corresponding authors: protein 1 or small inducible cytokine A2, is a cytokine from the CC chemokine family.
Cheng Deng It plays a crucial role in recruiting monocytes, memory T-cells, and dendritic cells to
(dengcheng2014@126.com) inflammatory sites resulting from tissue injury or infection. C-C motif chemokine
Mohammad Amjad Kamal
(ma.kamal@wchscu.cn) receptor 2 (CCR2) is a chemokine receptor that may influence lymphocyte function.
Shanshan Lai The interaction between CCL2 and CCR2 is essential for inflammatory responses
(lss7259@163.com) and cancer regulation, as it attracts monocytes and macrophages to tumor sites,
Citation: Kamal S, Ullah N, facilitating tumor growth and metastasis. Given the importance of CCL2 in regulating
Amanullah A, et al. Bioinformatics cell trafficking and cancer progression, we employed a bioinformatics approach to
approach to identifying potential
cancer-associated mutations examine the effects of oncogenic missense mutations in CCL2 on CCR2 activation.
in CCL2. Tumor Discov. We used precise computational methods to identify the molecular characteristics
2024;3(4):3891. responsible for the altered activity and interactions, thereby enhancing our
doi: 10.36922/td.3891 understanding of the molecular mechanisms underlying disease progression.
Received: June 7, 2024 We generated a three-dimensional model of the CCL2 protein with the identified
Accepted: September 5, 2024 mutations using the I-TASSER algorithm. The effects of these mutations on the
protein’s stability and functional properties were evaluated using various prediction
Published Online: October 21, 2024 tools, and molecular dynamics simulations were conducted using WebGro software.
Copyright: © 2024 Author(s). Our analysis of 83 CCL2 missense mutations identified 10 disease-causing mutations,
This is an Open-Access article including C59G, which was directly linked to cancer. The C59G mutation increases
distributed under the terms of the
Creative Commons Attribution the binding interaction between CCL2 and CCR2. The C59G position was determined
License, permitting distribution, to be highly conserved, and substitutions of cysteine (C) 59 with glycine (G) altered
and reproduction in any medium, CCL2 activity. Our results suggest that this mutation alters the CCL2–CCR2 binding
provided the original work is
properly cited. activity, lowering the risk of developing cancer and defending against pathogen
invasion during the neutrophil-mediated innate immune response.
Publisher’s Note: AccScience
Publishing remains neutral with
regard to jurisdictional claims in
published maps and institutional Keywords: CCL2; Molecular dynamic simulation; Colorectal cancer; Point mutation
affiliations.

Volume 3 Issue 4 (2024) 1 doi: 10.36922/td.3891