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个性化癌症治疗中的微小RNA

MicroRNAs in personalized cancer therapy.

作者信息

Sethi S, Ali S, Sethi S, Sarkar F H

机构信息

Department of Pathology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.

出版信息

Clin Genet. 2014 Jul;86(1):68-73. doi: 10.1111/cge.12362. Epub 2014 Mar 20.

Abstract

MicroRNAs (miRNAs) are small endogenous noncoding single-stranded RNAs. They critically regulate the post-transcriptional activity of several key physiological and pathological cell processes including cancer. Through their transcriptional regulatory functions, miRNAs control tumor proliferation, invasion and metastasis. The expression of miRNAs is altered in malignancies. It could be either upregulated or downregulated depending upon the role of a particular miRNA in the pathogenetic development of the tumor. The upregulated miRNAs exert an 'oncogenic' effect leading to tumor proliferation and metastasis. The downregulated miRNAs have 'tumor suppressor' effects. Recent studies have demonstrated that miRNAs have a role in the early diagnosis, prognosis and treatment outcome assessment of cancers. Every tumor has specific miRNA alterations, i.e. some are overexpressed and others are downregulated. These altered miRNAs can be used as a tumor-specific 'signature' for potential clinical use in improving the accuracy of diagnosis, determining prognosis and as therapeutic targets for therapy. Specific miRNAs can be targeted using oligonucleotide sequences corresponding to the altered miRNAs. These are referred to as 'antagomirs'. Depending upon the miRNA alterations in the tumor of an individual patient, one could design targeted therapies for personalized medicine in patients. Hence, miRNAs have an immense role in personalized cancer therapy.

摘要

微小RNA(miRNA)是一类内源性非编码单链小分子RNA。它们对包括癌症在内的多种关键生理和病理细胞过程的转录后活性起着至关重要的调节作用。通过其转录调控功能,miRNA控制肿瘤的增殖、侵袭和转移。在恶性肿瘤中,miRNA的表达会发生改变。根据特定miRNA在肿瘤发病机制中的作用,其表达可能上调或下调。上调的miRNA发挥“致癌”作用,导致肿瘤增殖和转移。下调的miRNA则具有“肿瘤抑制”作用。最近的研究表明,miRNA在癌症的早期诊断、预后及治疗效果评估中发挥作用。每种肿瘤都有特定的miRNA改变,即有些miRNA过度表达,而有些则下调。这些改变的miRNA可作为肿瘤特异性“标志物”,用于潜在的临床应用,以提高诊断准确性、确定预后并作为治疗靶点。可以使用与改变的miRNA对应的寡核苷酸序列靶向特定的miRNA。这些被称为“抗miR”。根据个体患者肿瘤中的miRNA改变情况,可以为患者设计个性化医疗的靶向治疗方案。因此,miRNA在个性化癌症治疗中发挥着巨大作用。

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