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致癌性微小RNA和肿瘤抑制基因3'非翻译区的遗传变异:癌症遗传学的新见解

Genetic variants in oncogenic miRNA and 3' untranslated region of tumor suppressor genes: emerging insight into cancer genetics.

作者信息

Choudhary Anita, Kumar Anil, Munshi Anjana

机构信息

Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda, India.

出版信息

Med Oncol. 2025 Jun 30;42(8):303. doi: 10.1007/s12032-025-02873-4.

Abstract

The miRNAs are key regulators of post-transcriptional gene expression. These are associated with the different molecular mechanisms which are engaged in the pathogenesis of various cancers, including breast cancer. The tumor suppressor and oncogenic miRNAs have a significant impact on cell proliferation, metastasis, angiogenesis, and apoptotic pathways. Variation in oncogenic miRNA encoding and the 3' UTR of the tumor suppressor genes associated with the development and prognosis of the cancer is being explored. These genetic variants alter oncogenic miRNAs' stability, target recognition, and binding ability, thereby resulting in the dysregulation of their target tumor suppressor gene, leading to uncontrolled cell division, a significant hallmark of cancer. The current review has been compiled to explore the genetic variation reported in the oncogenic miRNA encoding and 3' UTR of their target tumor suppressor genes associated with the development of breast cancer and its progression, focusing on the associated molecular mechanisms. Further, an effort has been made to discuss the possible therapeutic strategies, especially anti-miR, RNA interference, CRISPR/Cas, and ASOs, that have the potential to restore the function of the dysregulated tumor suppressor as well as oncogenic miRNA encoding genes.

摘要

微小RNA(miRNA)是转录后基因表达的关键调节因子。它们与参与包括乳腺癌在内的各种癌症发病机制的不同分子机制相关。肿瘤抑制性miRNA和致癌性miRNA对细胞增殖、转移、血管生成和凋亡途径具有重大影响。目前正在探索与癌症发展和预后相关的致癌性miRNA编码以及肿瘤抑制基因3'非翻译区(3'UTR)的变异。这些基因变异会改变致癌性miRNA的稳定性、靶标识别和结合能力,从而导致其靶标肿瘤抑制基因的失调,进而导致细胞不受控制地分裂,这是癌症的一个重要标志。本综述旨在探讨与乳腺癌发展及其进展相关的致癌性miRNA编码及其靶标肿瘤抑制基因3'UTR中报道的基因变异,并着重关注相关的分子机制。此外,还努力讨论了可能的治疗策略,特别是抗miR、RNA干扰、CRISPR/Cas和反义寡核苷酸(ASO),它们有可能恢复失调的肿瘤抑制基因以及致癌性miRNA编码基因的功能。

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