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沉默突变在KRAS突变型肿瘤中的作用。

Role of silent mutations in KRAS -mutant tumors.

作者信息

Lu Jun, Zhou Chao, Pan Feng, Liu Hongyu, Jiang Haohua, Zhong Hua, Han Baohui

机构信息

Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.

Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.

出版信息

Chin Med J (Engl). 2025 Feb 5;138(3):278-288. doi: 10.1097/CM9.0000000000003405. Epub 2024 Dec 10.

Abstract

Silent mutations within the RAS  gene have garnered increasing attention for their potential roles in tumorigenesis and therapeutic strategies. Kirsten-RAS ( KRAS ) mutations, predominantly oncogenic, are pivotal drivers in various cancers. While extensive research has elucidated the molecular mechanisms and biological consequences of active KRAS  mutations, the functional significance of silent mutations remains relatively understudied. This review synthesizes current knowledge on KRAS  silent mutations, highlighting their impact on cancer development. Silent mutations, which do not alter protein sequences but can affect RNA stability and translational efficiency, pose intriguing questions regarding their contribution to tumor biology. Understanding these mutations is crucial for comprehensively unraveling KRAS -driven oncogenesis and exploring novel therapeutic avenues. Moreover, investigations into the clinical implications of silent mutations in KRAS -mutant tumors suggest potential diagnostic and therapeutic strategies. Despite being in early stages, research on KRAS  silent mutations holds promise for uncovering novel insights that could inform personalized cancer treatments. In conclusion, this review underscores the evolving landscape of KRAS  silent mutations, advocating for further exploration to bridge fundamental biology with clinical applications in oncology.

摘要

RAS基因内的沉默突变因其在肿瘤发生和治疗策略中的潜在作用而受到越来越多的关注。 Kirsten-RAS(KRAS)突变主要是致癌性的,是各种癌症的关键驱动因素。虽然广泛的研究已经阐明了活性KRAS突变的分子机制和生物学后果,但沉默突变的功能意义仍相对研究不足。本综述综合了目前关于KRAS沉默突变的知识,强调了它们对癌症发展的影响。沉默突变不改变蛋白质序列,但可影响RNA稳定性和翻译效率,这就它们对肿瘤生物学的贡献提出了有趣的问题。了解这些突变对于全面揭示KRAS驱动的肿瘤发生和探索新的治疗途径至关重要。此外,对KRAS突变肿瘤中沉默突变的临床意义的研究提出了潜在的诊断和治疗策略。尽管尚处于早期阶段,但对KRAS沉默突变的研究有望揭示新的见解,为个性化癌症治疗提供依据。总之,本综述强调了KRAS沉默突变不断变化的格局,主张进一步探索,以将基础生物学与肿瘤学临床应用联系起来。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f58e/11771717/64950944870b/cm9-138-278-g001.jpg

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