ACTL6A: unraveling its prognostic impact and paving the way for targeted therapeutics in carcinogenesis

Refaat A Eid; Farag Mamdouh; Waleed K Abdulsahib; Dalal Sulaiman Alshaya; Fawziah A Al-Salmi; Maha Ali Alghamdi; Ibrahim Jafri; Eman Fayad; Ghadi Alsharif; Mohamed Samir A Zaki; Mohammed A Alshehri; Ahmed E Noreldin; Muhammad Alaa Eldeen

doi:10.3389/fmolb.2024.1387919

ACTL6A: unraveling its prognostic impact and paving the way for targeted therapeutics in carcinogenesis

Front Mol Biosci. 2024 May 30:11:1387919. doi: 10.3389/fmolb.2024.1387919. eCollection 2024.

Authors

Affiliations

¹ Pathology Department, College of Medicine, King Khalid University, Abha, Saudi Arabia.
² Biotechnology Division, Zoology Department, Faculty of Science, Benha University, Banha, Egypt.
³ Pharmacology and Toxicology Department, College of Pharmacy, Al Farahidi University, Baghdad, Iraq.
⁴ Department of Biology, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia.
⁵ Biology Department, College of Sciences, Taif University, Taif, Saudi Arabia.
⁶ Department of Biotechnology, College of Sciences, Taif University, Taif, Saudi Arabia.
⁷ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia.
⁸ Department of Biomedical Research, King Abdullah International Medical Research Center, Jeddah, Saudi Arabia.
⁹ Anatomy Department, College of Medicine, King Khalid University, Abha, Saudi Arabia.
¹⁰ Department of Child Health, College of Medicine, King Khalid University, Abha, Saudi Arabia.
¹¹ Department of Histology and Cytology, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Egypt.
¹² Cell Biology, Histology and Genetics Division, Zoology Department, Faculty of Science, Zagazig University, Zagazig, Egypt.

^# Contributed equally.

Abstract

Introduction: Increased Actin-like 6A (ACTL6A) expression is associated with various cancers, but its comprehensive investigation across different malignancies is lacking. We aimed to analyze ACTL6A as a potential oncogene and therapeutic target using bioinformatics tools. Methods: We comprehensively analyzed ACTL6A expression profiles across human malignancies, focusing on correlations with tumor grade, stage, metastasis, and patient survival. Genetic alterations were examined, and the epigenetic landscape of ACTL6A was assessed using rigorous methods. The impact of ACTL6A on immune cell infiltration in the tumor microenvironment was evaluated, along with molecular docking studies and machine learning models. Results: Our analysis revealed elevated ACTL6A expression in various tumors, correlating with poor prognostic indicators such as tumor grade, stage, metastasis, and patient survival. Genetic mutations and epigenetic modifications were identified, along with associations with immune cell infiltration and key cellular pathways. Machine learning models demonstrated ACTL6A's potential for cancer detection. Discussion: ACTL6A emerges as a promising diagnostic and therapeutic target in cancer, with implications for prognosis and therapy. Our study provides comprehensive insights into its carcinogenic actions, highlighting its potential as both a prognostic indicator and a target for anti-cancer therapy. This integrative approach enhances our understanding of ACTL6A's role in cancer pathogenesis and treatment.

Keywords: ACTL6A; carcinogenesis; oncogene; pan-cancer; prognosis.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The authors extend their appreciation to the Deanship of Scientific Research at King Khalid University for funding this work through a large group Research Project under grant number RGP2/17/44, and to the Deanship of Scientific Research at Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2024R465), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.