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口腔癌中的 microRNAs:从实验室走向临床,成为下一代医学。

microRNAs in oral cancer: Moving from bench to bed as next generation medicine.

机构信息

Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bengalore 560012, India.

Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bengalore 560012, India.

出版信息

Oral Oncol. 2020 Dec;111:104916. doi: 10.1016/j.oraloncology.2020.104916. Epub 2020 Jul 22.

Abstract

Oral cancer is the thirteenth most common cancer in the world, with India contributing to 33% of the global burden. Lack of specific non-invasive markers, non-improvement in patient survival and tumor recurrence remain a major clinical challenge in oral cancer. Epigenetic regulation in the form of microRNAs (miRs) that act as tumor suppressor miRs or oncomiRs has gained significant momentum with the advancement in the field, suggesting the potential for clinical application of miRs in oral cancer. The current review of literature identified miR-21, miR-27a(-3p), miR-31, miR-93, miR-134, miR-146, miR-155, miR-196a, miR-196b, miR-211, miR-218, miR-222, miR-372 and miR-373 to be up-regulated and let-7a, let-7b, let-7c, let-7d, let-7e, let-7f, let-7g, let-7i, miR-26a, miR-99a-5p, miR-137, miR-139-5p, miR-143-3p, miR-184 and miR-375 to be down-regulated in oral cancer. Mechanistic studies have uncovered several miRs that are deregulated at varying levels and in different stages of oral cancer progression, thus providing clinical utility in better diagnosis as well as usefulness in prognosis by identifying patients with poor prognosis or stratifying patients based on responsiveness to chemo- and radio-therapy. Lastly, exogenous modulation of miR expression using miRNA-based drugs in combination with first-line agents may be adopted as a new therapeutic modality to treat oral cancer. Knowledge of miRs and their involvement in key molecular processes, clinical association, responsiveness to therapy and clinical advancement may highlight additional avenues in order to improve patient morbidity and mortality. Furthermore, combinatorial approaches with miR-therapy may be efficacious in oral cancer.

摘要

口腔癌是全球第 13 常见的癌症,印度占全球负担的 33%。缺乏特异性的非侵入性标志物、患者生存率和肿瘤复发率没有提高,这些仍然是口腔癌的主要临床挑战。以肿瘤抑制 miRNA 或癌 miRNA 形式发挥作用的 miRNA 的表观遗传调控,随着该领域的进步,取得了显著进展,表明 miRNA 在口腔癌中的临床应用具有潜力。目前对文献的综述确定了 miR-21、miR-27a(-3p)、miR-31、miR-93、miR-134、miR-146、miR-155、miR-196a、miR-196b、miR-211、miR-218、miR-222、miR-372 和 miR-373 为上调,let-7a、let-7b、let-7c、let-7d、let-7e、let-7f、let-7g、let-7i、miR-26a、miR-99a-5p、miR-137、miR-139-5p、miR-143-3p、miR-184 和 miR-375 为下调。机制研究发现,miR 在口腔癌进展的不同水平和不同阶段存在失调,从而在改善诊断方面具有临床实用性,并通过识别预后不良的患者或根据对化疗和放疗的反应对患者进行分层,从而在预后方面具有有用性。最后,使用 miRNA 药物对 miR 表达进行外源性调节,与一线药物联合使用,可能成为治疗口腔癌的新治疗方法。miR 的知识及其在关键分子过程中的参与、临床相关性、对治疗的反应性以及临床进展,可能突出了更多的途径,以改善患者的发病率和死亡率。此外,miR 治疗的组合方法可能对口腔癌有效。

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