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反义长链非编码RNA KRT7-AS在胃癌中上调KRT7蛋白的分子机制及临床意义

反义长链非编码RNA KRT7-AS在胃癌中上调KRT7蛋白的分子机制及临床意义
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  • 批准号:81602082
  • 批准年度: 2016年
  • 学科分类:消化系统肿瘤(H1617) |
  • 项目负责人:黄滨滨
  • 负责人职称:医师
  • 依托单位:同济大学
  • 资助金额:18万元
  • 项目类别:青年科学基金项目
  • 研究期限:2017年01月01日 至 2019年12月31日
  • 中文关键词: 反义长链;非编码;RNA;KRT7-AS;KRT7
  • 英文关键词:KRT7-AS;antisense long non-coding RNA ;gastic cancer;proliferation;metastasis

项目摘要

中文摘要

长链非编码RNA在肿瘤中的功能和机制复杂多样,与多种肿瘤恶性增殖、转移相关。我们发现并命名了一胃癌来源的长链非编码RNA—KRT7-AS。它的高表达会促进胃癌细胞增殖以及淋巴结转移。它转录自DNA反义链,功能具有“位置特异性”,可通过核酸互补序列与正义链“伙伴”KRT7 mRNA形成RNA-RNA复合体,增加mRNA稳定性,间接增加KRT7蛋白表达。本研究中我们进一步推测KRT7-AS还具有转运功能,可以将KRT7 mRNA从核内转运到胞浆,并通过非互补序列(更确切的说是SINE重复)激活核糖体,增加KRT7蛋白翻译,使得少量的反义长链非编码RNA发挥充分作用。因此本研究旨在深入研究胃癌中KRT7-AS上调KRT7蛋白表达的分子机制,丰富反义长链非编码RNA的理论知识;并探讨它与胃癌增殖、转移以及预后等临床特点的关系,以期探索KRT7-AS作为早期识别胃癌恶性增殖转移分子标志物的可能性。

英文摘要

The role and mechanism of long non-coding RNA (lncRNA) in cancers is complicated and versatile. It involves in malignant proliferation and metastasis in several kinds of tumors. Recently, our group has studied lncRNAs in this context. We identified and named one long non-coding RNA (lncRNA) in gastric cancer (GC). In particular, KRT7-AS, which was greatly overexpressed in GC-derived cell lines and tissue specimens, and was significantly correlated with tumor size and lymph node metastasis in GC. KRT7-AS is also an antisense long non-coding RNA (AS lncRNA), which could exert function through its sense mRNA partner in a locus-specific manner. We found KRT7-AS upregulated its sense cognate partner gene, KRT7, by stabilizing its mRNA, leading to reduced mRNA degradation and increased KRT7 protein levels as well as promoting proliferation and metastasis in GC cells. Based on these previous findings, we now hypothesize that lncRNA KRT7-AS specifically targets KRT7 mRNA at its complementary sequence (i.e., its KRT7 mRNA-overlapping region), then “shuttles” KRT7 mRNA from the nucleus to the cytoplasmic polysome. Moreover, we also now posit that the non-complementary sequence of KRT7-AS (i.e., its non-KRT7 mRNA-overlapping region), more specifically SINE repeat within this sequence, activates the polysome to increase KRT7 protein translation. In summary, we now propose to elucidate the regulatory mechanism underlying KRT7-AS’s stimulation of KRT7 protein expression, which may rich the theory of AS lncRNA; to characterize the clinical significance of its promotion of cell proliferation and migration in GC, which may ultimately reveal the potential of KRT7-AS as a novel marker to early identify malignant proliferation and metastasis in GC.

评估说明

    国家自然科学基金项目“反义长链非编码RNA KRT7-AS在胃癌中上调KRT7蛋白的分子机制及临床意义”发布于爱科学iikx,并永久归类于相关科学基金导航中,仅供广大科研工作者查询、学习、选题参考。国科金是根据国家发展科学技术的方针、政策和规划,以及科学技术发展方向,面向全国资助基础研究和应用研究,发挥着促进我国基础研究源头创新的作用。国科金的真正价值在于它能否为科学进步和社会发展带来积极的影响。

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