Hsu Chou-Yi, Almajidi Yasir Qasim, Al-Hakeem Maher Abdulrazzaq, Alshahrani Mohammad Y, Nabil Wael, Jayakumar Sujayaraj Samuel, SinglaI Siya, Al-Khafaji Zahraa Abbas, Hussein Ahmed Remthan, Al-Mashhadani Zuhair I
Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
Department of pharmaceutics, College of Pharmacy, Alnahrain University, Baghdad, Iraq.
Semin Oncol. 2025 Oct;52(5):152395. doi: 10.1016/j.seminoncol.2025.152395. Epub 2025 Aug 12.
Cyclin-dependent kinases (CDKs) are a group of serine/threonine kinases that are at the center of cell cycle progression. Dysregulated CDK activity, found in a range of human cancers, leads to uncontrolled cell growth and development. Non-coding RNAs (ncRNAs), which include microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are emerging as critical regulators of gene expression and cellular processes, playing an important and often complex role in cancer development and progression. The purpose of this review is to organize knowledge about the interactions of ncRNAs with CDKs, contribution to cancer biology, and to discuss not only the different ways miRNAs target and downregulate CDKs mRNA, leading to inhibition of cell cycle progression and acting as tumor suppressors, but in the case of some miRNAs alter CDK activity as oncogenes by directly upregulating CDK expression or more frequently suppressing the expression of the canonical CDK inhibitors (p21 and p27). Moreover, long non-coding RNAs (lncRNAs) can regulate CDKs through a variety of mechanisms, such as functioning as molecular sponges by absorbing miRNAs that target CDK proteins as miRNA sponges, modulating CDK protein abundance and/or activity indirectly or directly (i.e., the direct interaction with the CDK proteins can potentially invoke an ability to regulate their stability, etc.). Circulating RNAs (circRNAs) also primarily modulate CDK levels and act as inhibitors of the appropriate CDK targeted by a miRNA sponge, potentially through direct interaction with a CDK. Overall, while our understanding of the ncRNA-CDK network is far from complete, the complexities surrounding ncRNA-CDK oncogenic developments and the ability to target these pathways offer significant promise in the harsh realities of cancerogenesis and further therapeutic interventions to fashion more precise cancer therapies that antagonize aberrant cell cycle progression in cancer subtypes.
细胞周期蛋白依赖性激酶（CDK）是一组丝氨酸/苏氨酸激酶，处于细胞周期进程的核心位置。在一系列人类癌症中发现的CDK活性失调会导致细胞不受控制地生长和发育。非编码RNA（ncRNA），包括微小RNA（miRNA）、长链非编码RNA（lncRNA）和环状RNA（circRNA），正逐渐成为基因表达和细胞过程的关键调节因子，在癌症的发生和发展中发挥着重要且往往复杂的作用。本综述的目的是整理有关ncRNA与CDK相互作用的知识，以及其对癌症生物学的贡献，并不仅讨论miRNA靶向和下调CDK mRNA从而抑制细胞周期进程并作为肿瘤抑制因子的不同方式，而且还讨论在某些情况下，一些miRNA通过直接上调CDK表达或更常见地抑制经典CDK抑制剂（p21和p27）的表达而作为癌基因改变CDK活性。此外，长链非编码RNA（lncRNA）可以通过多种机制调节CDK，例如通过吸收作为miRNA海绵靶向CDK蛋白的miRNA而作为分子海绵发挥作用，间接或直接调节CDK蛋白丰度和/或活性（即与CDK蛋白的直接相互作用可能引发调节其稳定性等的能力）。环状RNA（circRNA）也主要调节CDK水平，并作为miRNA海绵靶向的适当CDK的抑制剂，可能通过与CDK的直接相互作用来实现。总体而言，虽然我们对ncRNA-CDK网络的理解还远未完成，但围绕ncRNA-CDK致癌发展的复杂性以及靶向这些途径的能力，在癌症发生的严峻现实以及进一步的治疗干预中提供了巨大的希望，以制定更精确的癌症治疗方法来对抗癌症亚型中异常的细胞周期进程。
