Comprehensive multiomics and in silico approach uncovers prognostic, immunological, and therapeutic roles of ANLN in lung adenocarcinoma

• Published in: Functional & integrative genomics 2023-09, Vol.23 (3), p.223-223, Article 223
• Main Authors: Singh, Prithvi, Arora, Shweta, Beg, Md Amjad, Sahoo, Sibasis, Nayek, Arnab, Khan, Mohd Mabood, Sinha, Anuradha, Malik, Md. Zubbair, Athar, Fareeda, Serajuddin, Mohammad, Dohare, Ravins, Syed, Mansoor Ali
• Format: Article
• Language: English
• Subjects: Actin; active sites; Adenocarcinoma; Adenocarcinoma of Lung - drug therapy; Adenocarcinoma of Lung - genetics; Animal Genetics and Genomics; Biochemistry; Bioinformatics; Biomarkers; Biomedical and Life Sciences; Cancer; Cell Biology; Cell cycle; Cell proliferation; computer simulation; Flavonoids; genomics; High-throughput screening; Humans; hydrogen; Hydrogen bonding; Kaempferol; Kaempferols; Life Sciences; Lung cancer; lung neoplasms; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; lungs; Microbial Genetics and Genomics; microfilament proteins; Microfilament Proteins - metabolism; Molecular Docking Simulation; Molecular dynamics; Multiomics; Original Article; Plant Genetics and Genomics; plasticity; Prognosis; Survival analysis; therapeutics
• ISSN: 1438-793X; 1438-7948
• DOI: 10.1007/s10142-023-01144-7

The anillin actin-binding protein ( ANLN ) is immensely overexpressed in cancers, including lung cancer (LC). Phytocompounds have gained interest due to their broader potential and reduced unwanted effects. Screening numerous compounds presents a challenge, but in silico molecular docking is pragmatic. The present study aims to identify the role of ANLN in lung adenocarcinoma (LUAD), along with identification and interaction analysis of anticancer and ANLN inhibitory phytocompounds followed by molecular dynamics (MD) simulation. Using a systematic approach, we found that ANLN is significantly overexpressed in LUAD and mutated with a frequency of 3.73%. It is linked with advanced stages, clinicopathological parameters, worsening of relapse-free survival (RFS), and overall survival (OS), pinpointing its oncogenic and prognostic potential. High-throughput screening and molecular docking of phytocompounds revealed that kaempferol (flavonoid aglycone) interacts strongly with the active site of ANLN protein via hydrogen bonds, Vander Waals interactions, and acts as a potent inhibitor. Furthermore, we discovered that ANLN expression was found to be significantly higher ( p ) in LC cells compared to normal cells. This is a propitious and first study to demonstrate ANLN and kaempferol interactions, which might eventually lead to removal of rout from cell cycle regulation posed by ANLN overexpression and allow it to resume normal processes of proliferation. Overall, this approach suggested a plausible biomarker role of ANLN and the combination of molecular docking subsequently led to the identification of contemporary phytocompounds, bearing symbolic anticancer effects. The findings would be advantageous for pharmaceutics but require validation using in vitro and in vivo methods. Highlights • ANLN is significantly overexpressed in LUAD. • ANLN is implicated in the infiltration of TAMs and altering plasticity of TME. • Kaempferol (potential ANLN inhibitor) shows important interactions with ANLN which could remove the alterations in cell cycle regulation, imposed by ANLN overexpression eventually leading to normal process of cell proliferation.