Long non-coding RNA LUCAT1 promotes tumourigenesis by inhibiting ANXA2 phosphorylation in hepatocellular carcinoma
Long non-coding RNA LUCAT1 promotes tumourigenesis by inhibiting ANXA2 phosphorylation in hepatocellular carcinoma
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长非编码RNA LUCAT1通过抑制肝细胞癌中ANXA2磷酸化促进肿瘤发生
DOI：
10.1111/jcmm.14088
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发表时间：
2019-03-01
影响因子：
5.3
通讯作者：
Li, Guoqiang
中科院分区：
文献类型：
--
作者：
Lou, Yun;Yu, Yue;Li, Guoqiang
长非编码RNA(LncRNAs)在多种生物学过程中发挥着重要作用，然而，目前对肿瘤增殖和转移调控机制的了解还很有限。肺癌相关转录本1(LUCAT1)在多种人类癌症中已有报道，但其在肝细胞癌中的作用尚不清楚。本研究旨在探讨LUCAT1在肝癌细胞和临床标本中的生物学作用及其机制。我们的结果表明，LUCAT1在肝癌组织和细胞中表达上调。功能丧失和功能获得的研究表明，LUCAT1在体内和体外都能促进肝癌细胞的增殖和转移。此外，RNA下拉和Western印迹分析表明，LUCAT1抑制Annexin A2(ANXA2)的磷酸化，从而减少ANXA2-S100A10异四聚体(AIIt)的降解，进而加速纤溶酶原向纤溶酶的分泌，从而导致金属蛋白酶蛋白的激活。综上所述，我们认为LUCAT1可作为一种新的肝癌诊断和治疗靶点。
Long non-coding RNAs (lncRNAs) play essential roles in diverse biological processes; however, current understanding of the mechanism underlying the regulation of tumour proliferation and metastasis is limited. Lung cancer-associated transcript 1 (LUCAT1) has been reported in a variety of human cancers, while its role in hepatocellular carcinoma (HCC) remains unclear. This study aimed to determine the biological role and underlying mechanism of LUCAT1 on progression and metastasis in HCC cells and clinical specimens. Our results demonstrated that LUCAT1 was up-regulated in HCC tissues and cells. Loss- and gain-of-function studies revealed that LUCAT1 promotes the proliferation and metastasis of HCC cells in vitro and in vivo. Furthermore, RNA pulldown and Western blot assays indicated that LUCAT1 inhibited the phosphorylation of Annexin A2 (ANXA2) to reduce the degradation of ANXA2-S100A10 heterotetramer (AIIt), which in turn accelerated the secretion of plasminogen into plasmin, thereby resulting in the activation of metalloprotease proteins. In conclusion, we propose that LUCAT1 serves as a novel diagnostic and therapeutic target for HCC.