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多种癌种中常见和独特的 microRNAs 调控相似的通路网络来介导癌症进展。

Common and Unique microRNAs in Multiple Carcinomas Regulate Similar Network of Pathways to Mediate Cancer Progression.

机构信息

Department of Biological Sciences, Birla Institute of Technology and Science (BITS), Pilani Campus, Pilani, Rajasthan, India.

出版信息

Sci Rep. 2020 Feb 11;10(1):2331. doi: 10.1038/s41598-020-59142-9.

Abstract

Cancer is a complex disease with a fatal outcome. Early detection of cancer, by monitoring appropriate molecular markers is very important for its therapeutic management. In this regard, the short non-coding RNA molecules, microRNAs (miRNAs) have shown great promise due to their availability in circulating fluids facilitating non-invasive detection of cancer. In this study, an in silico comparative analysis was performed to identify specific signature miRNAs dysregulated across multiple carcinomas and simultaneously identify unique miRNAs for each cancer type as well. The miRNA-seq data of cancer patient was obtained from GDC portal and their differential expressions along with the pathways regulated by both common and unique miRNAs were analyzed. Our studies show twelve miRNAs commonly dysregulated across seven different cancer types. Interestingly, four of those miRNAs (hsa-mir-210, hsa-mir-19a, hsa-mir-7 and hsa-mir-3662) are already reported as circulatory miRNAs (circRNAs); while, the miR-183 cluster along with hsa-mir-93 have been found to be incorporated in exosomes signifying the importance of the identified miRNAs for their use as prospective, non-invasive biomarkers. Further, the target mRNAs and pathways regulated by both common and unique miRNAs were analyzed, which interestingly had significant commonality. This suggests that miRNAs that are commonly de-regulated and specifically altered in multiple cancers might regulate similar pathways to promote cancer. Our data is of significance because we not only identify a set of common and unique miRNAs for multiple cancers but also highlight the pathways regulated by them, which might facilitate the development of future non-invasive biomarkers conducive for early detection of cancers.

摘要

癌症是一种具有致命后果的复杂疾病。通过监测适当的分子标志物早期发现癌症对于其治疗管理非常重要。在这方面,短链非编码 RNA 分子 miRNA 由于其在循环液中的可用性,为癌症的非侵入性检测提供了便利,因此具有很大的应用前景。在这项研究中,我们进行了计算机模拟比较分析,以确定在多种癌症中失调的特定特征 miRNA,并同时识别每种癌症类型的独特 miRNA。从 GDC 门户获取癌症患者的 miRNA-seq 数据,并分析其差异表达以及共同和独特 miRNA 调节的途径。我们的研究表明,在七种不同的癌症类型中,有 12 个 miRNA 普遍失调。有趣的是,其中四个 miRNA(hsa-mir-210、hsa-mir-19a、hsa-mir-7 和 hsa-mir-3662)已经被报道为循环 miRNA(circRNAs);而 miR-183 簇与 hsa-mir-93 已被发现被包裹在 exosomes 中,这表明所鉴定的 miRNA 对于它们作为有前途的非侵入性生物标志物的重要性。此外,我们还分析了共同和独特 miRNA 调节的靶 mRNA 和途径,有趣的是,它们具有显著的共性。这表明,在多种癌症中普遍失调和特异性改变的 miRNA 可能调节相似的途径以促进癌症的发生。我们的数据具有重要意义,因为我们不仅确定了一组用于多种癌症的共同和独特 miRNA,还强调了它们调节的途径,这可能有助于开发未来有利于癌症早期检测的非侵入性生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca99/7012856/f38c4ccc3b69/41598_2020_59142_Fig1_HTML.jpg

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