Ragunath Muthu, Shen Aling, Wei Lin, Peng Jun, Thiruvengadam Muthu
Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea.
Fujian Key Laboratory of Integrative Medicine in Geriatrics, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China.
Curr Pharm Des. 2024;30(37):2911-2921. doi: 10.2174/0113816128301870240730071910.
Post-transcriptional modifications (PTMs) are pivotal in the regulation of gene expression, and pseudouridylation is emerging as a critical player. This modification, facilitated by enzymes such as NOB1 (PNO1), is integral to ribosome biogenesis. PNO1, in collaboration with the NIN1/RPN12 binding protein 1 homolog (NOB1), is vital for the maturation of ribosomes, transitioning 20S pre-rRNA into functional 18S rRNA. Recent studies have highlighted PNO1's potential involvement in cancer progression; however, its underlying mechanisms remain unclear. Relentless growth characterizing cancer underscores the burgeoning significance of epitranscriptomic modifications, including pseudouridylation, in oncogenesis. Given PNO1's emerging role, it is imperative to delineate its contribution to cancer development to identify novel therapeutic interventions. This review summarizes the current literature regarding the role of PNO1 in cancer progression and its molecular underpinnings in oncogenesis. Overexpression of PNO1 was associated with unfavorable prognosis and increased tumor malignancy. At the molecular level, PNO1 facilitates cancer progression by modulating mRNA stability, alternative splicing, and translation efficiency. Its role in pseudouridylation of oncogenic and tumor-suppressor transcripts further underscores its significance in cancer biology. Although disruption of ribosome biogenesis is known to precipitate oncogenesis, the precise mechanisms by which these alterations contribute to cancer remain unclear. This review elucidates the intricate process of ribosomal small subunit maturation, highlighting the roles of crucial ribosomal proteins (RPs) and RNA-binding proteins (RBPs) as well as the positioning and function of NOB1 and PNO1 within the 40S subunit. The involvement of these components in the maturation of the small subunit (SSU) and their significance in the context of cancer therapeutics has been thoroughly explored. PNO1's burgeoning significance in oncology makes it a potential target for cancer therapies. Strategies aimed at modulating PNO1-mediated pseudouridylation may provide new avenues for cancer treatment. However, further research is essential to unravel the complete spectrum of PNO1 mechanisms in cancer and harness this knowledge for the development of targeted and more efficacious anticancer therapies.
转录后修饰（PTMs）在基因表达调控中起着关键作用，而假尿苷化正成为一个关键因素。这种修饰由诸如NOB1（PNO1）等酶催化，是核糖体生物合成所必需的。PNO1与NIN1/RPN12结合蛋白1同源物（NOB1）协同作用，对核糖体的成熟至关重要，可将20S前体rRNA转化为功能性18S rRNA。最近的研究强调了PNO1在癌症进展中的潜在作用；然而，其潜在机制仍不清楚。癌症的持续生长凸显了表观转录组修饰（包括假尿苷化）在肿瘤发生中日益增长的重要性。鉴于PNO1的新出现的作用，必须阐明其对癌症发展的贡献，以确定新的治疗干预措施。本综述总结了当前关于PNO1在癌症进展中的作用及其在肿瘤发生中的分子基础的文献。PNO1的过表达与不良预后和肿瘤恶性程度增加有关。在分子水平上，PNO1通过调节mRNA稳定性、可变剪接和翻译效率促进癌症进展。它在致癌和抑癌转录本的假尿苷化中的作用进一步强调了其在癌症生物学中的重要性。虽然已知核糖体生物合成的破坏会引发肿瘤发生，但这些改变导致癌症的确切机制仍不清楚。本综述阐明了核糖体小亚基成熟的复杂过程，强调了关键核糖体蛋白（RPs）和RNA结合蛋白（RBPs）的作用以及NOB1和PNO1在40S亚基中的定位和功能。这些成分在小亚基（SSU）成熟中的参与及其在癌症治疗背景下的意义已得到充分探索。PNO1在肿瘤学中日益增长的重要性使其成为癌症治疗的潜在靶点。旨在调节PNO1介导的假尿苷化的策略可能为癌症治疗提供新途径。然而，进一步的研究对于揭示PNO1在癌症中的完整机制谱并利用这些知识开发有针对性和更有效的抗癌疗法至关重要。
