长链非编码RNA HOTAIR在恶性肿瘤中的研究进展
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中南大学肿瘤研究所,中南大学肿瘤研究所,中南大学肿瘤研究所,中南大学肿瘤研究所,中南大学肿瘤研究所,中南大学肿瘤研究所,中南大学肿瘤研究所,中南大学湘雅三医院,中南大学湘雅三医院,中南大学,中南大学肿瘤研究所,中南大学肿瘤研究所

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国家级大学生创新创业项目(201310533063),中南大学校级大学生创新创业项目(CY14283,CY14284),中南大学本科生自由探索项目(2282014bks197)和湖南省自然科学基金(14JJ1010, 2015JJ1022)资助项目


Progress of Long Noncoding RNA HOTAIR in Human Cancer
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Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education,Cancer Research Institute,Central South University,Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education,Cancer Research Institute,Central South University,Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education,Cancer Research Institute,Central South University,Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education,Cancer Research Institute,Central South University,Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education,Cancer Research Institute,Central South University,Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education,Cancer Research Institute,Central South University,Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education,Cancer Research Institute,Central South University,Hunan Key Laboratory of Nonresolving Inflammation and Cancer,Disease Genome Research Center,The Third Xiangya Hospital,Central South University,Hunan Provincial Tumor Hospital and The Affiliated Tumor Hospital of Xiangya Medical School,Central South University,Hunan Provincial Tumor Hospital and The Affiliated Tumor Hospital of Xiangya Medical School,Central South University,Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education,Cancer Research Institute,Central South University,Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education,Cancer Research Institute,Central South University;China;Hunan Key Laboratory of Nonresolving Inflammation and Cancer,Disease Genome Research Center,The Third Xiangya Hospital,Central South University;China;Hunan Provincial Tumor Hospital and The Affiliated Tumor Hospital of Xiangya Medical School,Central South University;China

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This work was supported by grants from The National College Students' Innovation and Entrepreneurship Training Program of China (201310533063), The Students' Innovation and Entrepreneurship Training Program of Central South University (CY14283, CY14284) , The Free Exploration Program of Central South University (2282014bks197), and The Natural Science Foundation of Hunan Province (14JJ1010, 2015JJ1022)

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    摘要:

    长链非编码RNA(long noncoding RNA,lncRNA) 与恶性肿瘤的发生发展密切相关.HOX转录反义RNA(HOX transcript antisense RNA,HOTAIR)是第一个被发现具有反式调控作用的lncRNA.目前发现HOTAIR在多种肿瘤中表达上调,且HOTAIR的高表达与不良预后密切相关.研究发现HOTAIR可通过与甲基化酶复合体PRC2共同作用,调控组蛋白H3第27位赖氨酸的三甲基化(histone H3 tri-methylated at lysine 27,H3K27me3),从而影响WIF1、PTEN、p21等基因的表达,并通过这些基因调控Wnt、Akt及p53等信号通路,从而在肿瘤的细胞周期、凋亡、血管生成、侵袭与转移等过程中发挥重要功能.进一步研究HOTAIR在肿瘤中的作用机制,对深入了解恶性肿瘤的病因发病学具有重要理论意义,同时,HOTAIR作为分子标记或者潜在的靶点,在恶性肿瘤的早期诊断、疗效判断、预后预测,乃至基因治疗等方面也将具有广阔的临床应用前景.

    Abstract:

    Long noncoding RNA (lncRNA) play important roles in cancer progression. HOX transcript antisense RNA (HOTAIR) was observed upregulated in a variety of tumors. Over-expression of HOTAIR is a poor prognostic factor. HOTAIR interacts with Polycomb Repressive complex 2 (PRC2), resulting in histone H3 tri-methylated atlysine27 (H3K27me3), which silences the expression of some down-stream genes, such as WIF-1, PTEN and p21, then mediated Wnt, Akt and p53 signaling pathways transduction. As a result, the properties of tumor, including invasion and metastasis, evading growth suppressors, resisting apoptosis and inducing angiogenesis would be affected. Thoroughly elucidate mechanisms of HOTAIR in cancer development will have important theoretical significance in cancer etiology and pathogenesis. As an important biomarker and potential target, HOTAIR may also has important clinical application in cancer's early diagnosis, therapeutic evaluation, prognosis, and even potential gene therapy.

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李雨薇,王裕民,张雪莹,薛 丹,邝 彪,潘序雅,荆益州,李小玲,周 鸣,熊 炜,曾朝阳,李桂源.长链非编码RNA HOTAIR在恶性肿瘤中的研究进展[J].生物化学与生物物理进展,2015,42(3):228-235

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历史
  • 收稿日期:2014-08-14
  • 最后修改日期:2014-11-29
  • 接受日期:2014-12-03
  • 在线发布日期: 2015-03-24
  • 出版日期: 2015-03-20