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ORIGINAL RESEARCH ARTICLE

Bioinformatics approach to identifying potential cancer-associated mutations in CCL2

Shah Kamal1† ,  Najeeb Ullah1† ,  Amanullah Amanullah1 ,  Mariam Ahmed Mujtaba2 ,  Kashif Ali Khan3 ,  Cheng Deng1* ,  Shanshan Lai1* ,  Mohammad Amjad Kamal4,5,6,7,8*
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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
7 Centre for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
8 Enzymoics, 7 Peterlee Place, Hebersham, Novel Global Community Educational Foundation, NSW, Australia
Tumor Discovery 2024, 3(4), 3891 https://doi.org/10.36922/td.3891
Submitted: 7 June 2024 | Accepted: 5 September 2024 | Published: 21 October 2024
(This article belongs to the Special Issue Colorectal Cancer: Best Tools for Diagnosis to Management Strategies)
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Chemokine C-C motif ligand 2 (CCL2), also known as monocyte chemoattractant protein 1 or small inducible cytokine A2, is a cytokine from the CC chemokine family. It plays a crucial role in recruiting monocytes, memory T-cells, and dendritic cells to inflammatory sites resulting from tissue injury or infection. C-C motif chemokine receptor 2 (CCR2) is a chemokine receptor that may influence lymphocyte function. The interaction between CCL2 and CCR2 is essential for inflammatory responses and cancer regulation, as it attracts monocytes and macrophages to tumor sites, facilitating tumor growth and metastasis. Given the importance of CCL2 in regulating cell trafficking and cancer progression, we employed a bioinformatics approach to examine the effects of oncogenic missense mutations in CCL2 on CCR2 activation. We used precise computational methods to identify the molecular characteristics responsible for the altered activity and interactions, thereby enhancing our understanding of the molecular mechanisms underlying disease progression. We generated a three-dimensional model of the CCL2 protein with the identified mutations using the I-TASSER algorithm. The effects of these mutations on the protein’s stability and functional properties were evaluated using various prediction tools, and molecular dynamics simulations were conducted using WebGro software. Our analysis of 83 CCL2 missense mutations identified 10 disease-causing mutations, including C59G, which was directly linked to cancer. The C59G mutation increases the binding interaction between CCL2 and CCR2. The C59G position was determined to be highly conserved, and substitutions of cysteine (C) 59 with glycine (G) altered CCL2 activity. Our results suggest that this mutation alters the CCL2–CCR2 binding activity, lowering the risk of developing cancer and defending against pathogen invasion during the neutrophil-mediated innate immune response.

Keywords
CCL2
Molecular dynamic simulation
Colorectal cancer
Point mutation
Funding
This work was supported by National Natural Science Foundation of China (32270438, 32170498, 31970388), the National Key Research and Development Program of China (2021YFF0702000, 2018YFD0900602), 1.3+.5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYJC21050), the Science and Technology Department of Sichuan Province (2022YFH0116), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), the National Clinical Research Center for Geriatrics, West China Hospital, and Sichuan University (Z2023JC003).
Conflict of interest
Mohammad Amjad Kamal is the Guest Editor of this special issue, but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
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Tumor Discovery, Electronic ISSN: 2810-9775 Print ISSN: 3060-8597, Published by AccScience Publishing
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