Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Biomed Pharmacother. 2024 Jul;176:116833. doi: 10.1016/j.biopha.2024.116833. Epub 2024 Jun 5.
Lung cancer poses a significant challenge regarding molecular heterogeneity, as it encompasses a wide range of molecular alterations and cancer-related pathways. Recent discoveries made it feasible to thoroughly investigate the molecular mechanisms underlying lung cancer, giving rise to the possibility of novel therapeutic strategies relying on molecularly targeted drugs. In this context, forkhead box O3 (FOXO3), a member of forkhead transcription factors, has emerged as a crucial protein commonly dysregulated in cancer cells. The regulation of the FOXO3 in reacting to external stimuli plays a key role in maintaining cellular homeostasis as a component of the molecular machinery that determines whether cells will survive or dies. Indeed, various extrinsic cues regulate FOXO3, affecting its subcellular location and transcriptional activity. These regulations are mediated by diverse signaling pathways, non-coding RNAs (ncRNAs), and protein interactions that eventually drive post-transcriptional modification of FOXO3. Nevertheless, while it is no doubt that FOXO3 is implicated in numerous aspects of lung cancer, it is unclear whether they act as tumor suppressors, promotors, or both based on the situation. However, FOXO3 serves as an intriguing possible target in lung cancer therapeutics while widely used anti-cancer chemo drugs can regulate it. In this review, we describe a summary of recent findings on molecular mechanisms of FOXO3 to clarify that targeting its activity might hold promise in lung cancer treatment.
肺癌在分子异质性方面构成了重大挑战，因为它包含了广泛的分子改变和与癌症相关的途径。最近的发现使得深入研究肺癌的分子机制成为可能，从而产生了依赖于分子靶向药物的新治疗策略的可能性。在这种情况下，叉头框 O3（FOXO3）作为叉头转录因子的成员，已成为癌细胞中普遍失调的关键蛋白。FOXO3 对外部刺激的反应调节在维持细胞内稳态方面起着关键作用，作为决定细胞是存活还是死亡的分子机制的一部分。事实上，各种外在信号调节 FOXO3，影响其亚细胞定位和转录活性。这些调节是通过多种信号通路、非编码 RNA（ncRNA）和蛋白相互作用介导的，最终导致 FOXO3 的转录后修饰。然而，尽管毫无疑问 FOXO3 参与了肺癌的许多方面，但根据具体情况，它是否作为肿瘤抑制因子、促进因子或两者兼而有之尚不清楚。然而，FOXO3 作为肺癌治疗的一个有趣的潜在靶点，而广泛使用的抗癌化疗药物可以调节它。在这篇综述中，我们描述了 FOXO3 分子机制的最新研究结果，以阐明靶向其活性可能在肺癌治疗中具有前景。
