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整合 miRNA 分析鉴定出 hsa-miR-3154、hsa-miR-7-3 和 hsa-miR-600 作为宫颈癌潜在的预后生物标志物。

Integrative miRNA analysis identifies hsa-miR-3154, hsa-miR-7-3, and hsa-miR-600 as potential prognostic biomarker for cervical cancer.

机构信息

Department of Gynaecology and Obstetrics, The Second People's Hospital of Jingmen, Jingmen, Hubei, China.

Department of Gynaecology and Obstetrics, Huai'an Second People's Hospital and The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, Jiangsu, China.

出版信息

J Cell Biochem. 2018 Feb;119(2):1558-1566. doi: 10.1002/jcb.26315. Epub 2017 Sep 7.

Abstract

MicroRNAs, which can interfere with the translation of target mRNAs, caught a particular interest as their functions are related to human cancers. As the most common cancer in women, cervical cancer remains one of the leading cancer-related causes of death. In this study, we performed an integrative miRNA analysis to identify prognosis related miRNAs for cervical cancer. In addition, we developed an n-miRNA expression signature (risk score) to comprehensively assess the prognosis of cervical cancer, especially for survival time. Furthermore, we performed target predictions and functional enrichment analyses for the identified miRNAs to investigate their potential role in the development of disease. Univariate Cox regression models were used to assess the association between miRNAs and prognosis of cervical cancer. Three miRNAs were identified to be significantly associated with survival time of patients. Hsa-miR-3154 and hsa-miR-7-3 were significantly associated with shortened survival time and more death cases, whereas expression level of hsa-miR-600 was significantly associated with prolonged survival time. The function enrichment analysis showed the target genes of poor prognosis related miRNAs were mainly enriched in the mTOR pathway, whereas target genes of positive prognosis related miRNAs were mainly enriched in the AMPK pathway. In summary, a 3-miRNA expression signature was identified which can predict cervical cancer patient survival. The potential functions of this 3-miRNA expression signature and individual miRNAs as prognostic targets of cervical cancer were revealed by this study. Furthermore, these findings may have important implications in the understanding of the potential therapeutic method for the cervical cancer patients.

摘要

微小 RNA(miRNA)可以干扰靶 mRNA 的翻译,其功能与人类癌症有关,因此引起了特别关注。宫颈癌是女性最常见的癌症,仍然是癌症相关死亡的主要原因之一。在这项研究中,我们进行了 miRNA 的综合分析,以鉴定与宫颈癌相关的预后 miRNA。此外,我们开发了一种 n-miRNA 表达特征(风险评分),以全面评估宫颈癌的预后,特别是生存时间。此外,我们对鉴定出的 miRNA 进行了靶基因预测和功能富集分析,以研究它们在疾病发展中的潜在作用。单变量 Cox 回归模型用于评估 miRNA 与宫颈癌预后之间的关联。有 3 个 miRNA 与患者的生存时间显著相关。hsa-miR-3154 和 hsa-miR-7-3 与缩短生存时间和更多死亡病例显著相关,而 hsa-miR-600 的表达水平与延长生存时间显著相关。功能富集分析显示,预后不良相关 miRNA 的靶基因主要富集在 mTOR 通路中,而预后良好相关 miRNA 的靶基因主要富集在 AMPK 通路中。综上所述,本研究鉴定了一个 3-miRNA 表达特征,可以预测宫颈癌患者的生存。本研究揭示了该 3-miRNA 表达特征和个体 miRNA 作为宫颈癌预后靶标的潜在功能。此外,这些发现可能对理解宫颈癌患者的潜在治疗方法具有重要意义。

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