Abstract：
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.
摘要：
Anillin肌动蛋白结合蛋白（ANLN）在癌症中过度表达，包括肺癌（LC）。植物化合物由于其更广泛的潜力和减少的不希望的影响而获得了兴趣。筛选众多的化合物提出了一个挑战，但在硅分子对接是务实的。本研究旨在确定ANLN在肺腺癌（LUAD）中的作用。以及抗癌和ANLN抑制性植物化合物的鉴定和相互作用分析，然后进行分子动力学（MD）模拟。使用系统的方法，我们发现ANLN在LUAD中显著过表达，突变频率为3.73%。它与高级阶段有关，临床病理参数，无复发生存率（RFS）恶化，和总生存率（OS），查明其致癌和预后潜力。植物化合物的高通量筛选和分子对接表明山奈酚（类黄酮苷元）通过氢键与ANLN蛋白的活性位点相互作用强烈，范德瓦尔斯互动，并作为一种有效的抑制剂。此外，我们发现与正常细胞相比,LC细胞中的ANLN表达显著更高(p)。这是一个有利的和第一个研究证明ANLN和山奈酚的相互作用，这可能最终导致从ANLN过表达引起的细胞周期调节中去除rout，并使其恢复正常的增殖过程。总的来说,这种方法提出了一个合理的生物标志物的作用，ANLN和分子对接的组合，随后导致当代植物化合物的鉴定，具有象征性的抗癌作用。该发现对于药剂学将是有利的,但需要使用体外和体内方法进行验证。要点:•ANLN在LUAD中显著过表达。•ANLN与TAM的渗透和改变TME的可塑性有关。•山奈酚（潜在的ANLN抑制剂）显示与ANLN的重要相互作用，可以消除细胞周期调节的改变，由ANLN过表达最终导致细胞增殖的正常过程。
