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Mol Cell:研究鉴定出促进肝癌发展的靶基因!

2017-08-23 sunshine2015 Medicalxpress

调控肝细胞代谢并抑制肝癌发展的分子的新研究表明,该分子与肝细胞中数千个基因相互作用,当分子水平下降时,其通常发生在肝癌发展过程中,某些促癌基因的活性升高。

【研究鉴定肝癌的基因靶点,将基因与患者生存率联系起来】调控肝细胞代谢并抑制肝癌发展的分子的新研究表明,该分子与肝细胞中数千个基因相互作用,当分子水平下降时,其通常发生在肝癌发展过程中,某些促癌基因的活性升高。

研究结果可能有一天可以帮助医生更好地预测肝癌患者的生存,并帮助确定称为microRNA-122(miR-122)的分子是否应开发为抗癌药物。

该研究报告发表在“分子细胞”杂志上,由俄亥俄州立大学综合癌症中心 - 亚瑟·詹姆斯癌症医院和理查德·佐夫罗研究所(OSUCCC - James)及洛克菲勒大学霍华德·休斯医学研究所的研究人员领导。

研究人员试图在生物化学方面定义肝脏中最常见形式的肝脏和肝细胞癌(HCC)中的所有miR-122靶位点,并了解哪些靶基因对肝癌发展或进展至关重要。 miR-122几乎完全在肝细胞中发现,其作用包括调节胆固醇和脂质代谢。

研究人员在小鼠模型中发现了超过11,000个miR-122结合位点。他们进一步发现:

·miR-122靶向人类近4,800个基因;

·其中965只与小鼠相同;

·在共同的目标中,大多数在患者的HCC肿瘤组织中更高表达;

·HCC中miR-122的缺失导致某些癌症相关基因的过度表达。

·肿瘤组织中三种保守靶基因BCL9,SLC52A2和STX6的水平升高可预测人类HCC患者的生存率差。

共同主要研究者和OSUCCC - 詹姆斯研究员Kalpana Ghoshal博士说:“我们的目标是了解miR-122如何调节肝脏代谢并抑制癌症发展,并确定可能参与HCC发展的人类和小鼠的共同靶点。“这种知识对于确定该分子是否应该作为肝癌的可能治疗剂来开发至关重要。”

Ghoshal补充说,研究结果显着扩大了早期研究鉴定的miR-122结合位点的数量,因为研究者使用的方法鉴定了其他技术缺失的位点。 (注:一个基因可以有多个microRNA靶位点。)

对于这项研究,Ghoshal和她的同事们使用了缺少miR-122的小鼠模型,以及正常小鼠;来自9个HCC患者的肝癌组织和正常肝组织;以及集中373例HCC患者的肝癌细胞癌数据资料的“癌症基因组图谱”。

其他主要发现包括:

·虽然miR-122是高度保守的(它存在于从鱼到人的肝细胞中),但是大部分miR-122靶点是物种特异性的;

·研究结果显示早期研究错过的结合位点;需要确定miR-122与附加位点结合的结果;

·人类HCC具有核心的一组保守的miR-122结合位点。

原始出处:Luna JM, Barajas JM, Teng KY, et al. Argonaute CLIP Defines a Deregulated miR-122-Bound Transcriptome that Correlates with Patient Survival in Human Liver Cancer. Mol Cell. 2017 Aug 3;67(3):400-410.e7. 

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    2018-05-29 维他命
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    2017-08-23 changjiu

    学习了.谢谢

    0

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    2017-08-23 131****1460

    学习了受益匪浅.

    0

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Radiology:临门静脉或肝静脉主干的恶性肝肿瘤无法热消融怎么办?

射频消融治疗是一种肝癌微创治疗方法,借助于超声等影像技术引导将射频电极针直接插入肝肿瘤内,通过射频能量使病灶局部组织产生高温,最终使肿瘤凝固坏死和灭活。本研究旨在探究不可逆性电穿孔技术(IRE)在治疗非热消融(射频消融(RFA)或微波消融)的肝癌的效能和安全性,并将结果发表在Radiology上。

远离肝癌,口服抗乙肝病毒药物该如何用?

口服核苷(酸)类似物在慢性乙型肝炎抗病毒治疗中的"有效性"、"可行性"、"安全性"已获得临床的广泛认同,其显着改善了慢性乙肝和乙肝肝硬化患者的预后,提高了患者的生活质量,但患者对核苷(酸)类抗乙肝病毒药物的使用及认识上有一些误区,本文根据指南及文献,对一些患者的常见用药问题进行解惑。

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