SSRP1 Contributes to the Malignancy of Hepatocellular Carcinoma and Is Negatively Regulated by miR-497.
SSRP1 Contributes to the Malignancy of Hepatocellular Carcinoma and Is Negatively Regulated by miR-497.
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SSRP1 导致肝细胞癌的恶性，并受到 miR-497 的负调控。
DOI：
10.1038/mt.2016.9
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发表时间：
2016-05
期刊：
影响因子：
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通讯作者：
Xiang G
中科院分区：
文献类型：
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作者：
Ding Q;He K;Luo T;Deng Y;Wang H;Liu H;Zhang J;Chen K;Xiao J;Duan X;Huang R;Xia Z;Zhou W;He J;Yu H;Jiao X;Xiang G
本研究旨在阐明结构特异性识别蛋白1(SSRP1)在肝细胞癌中的临床意义和功能作用，并探讨其在肿瘤中异常高表达的可能机制。在目前的研究中，我们证实了SSRP1在肝细胞癌样本中上调。我们还发现它的表达上调与几个临床病理特征有关，如血清AFP水平高、肿瘤体积大、肝细胞癌患者的T分期高，其高表达提示总生存期短、复发快。为了研究SSRP1在肝细胞癌进展中的作用，我们建立了损失函数模型和增益函数模型。我们证明了SSPR1在体内外对肝癌细胞的增殖和转移均有调节作用。此外，我们还证明了SSRP1调控的细胞凋亡过程及其基因敲除增加了肝癌细胞对阿霉素、5-氟尿嘧啶和顺铂的敏感性。我们还发现microRNA-497(miR-497)是SSRP1的转录后调控因子。异位表达miR-497在信使RNA和蛋白质水平上均抑制了3‘-非翻译区偶联荧光素酶活性和内源SSRP1的表达。我们首次证明了SSRP1上调有助于肝细胞癌的发生，并且抑制肿瘤的miR-497作为其负调控因子。
The aim of this study is to clarify the clinical implication and functional role of structure specific recognition protein 1 (SSRP1) in hepatocellular carcinoma (HCC) and explore the underlying mechanism of aberrant high expression of SSRP1 in cancers. In the present investigation, we validated that SSRP1 was upregulated in HCC samples. We also demonstrated that its upregulation was associated with several clinicopathologic features such as higher serum AFP level, larger tumor size, and higher T stage of HCC patients; and its high expression indicated shorter overall survival and faster recurrence. To investigate the role of SSRP1 in HCC progression, both loss- and gain-function models were established. We demonstrated that SSPR1 modulated both proliferation and metastasis of HCC cells in vitro and vivo. Furthermore, we demonstrated that SSRP1-modulated apoptosis process and its knockdown increased the sensitivity of HCC cells to doxorubicin, 5-Fluorouracil, and cisplatin. We also identified microRNA-497 (miR-497) as a posttranscriptional regulator of SSRP1. Ectopic expression of miR-497 inhibited 3'-untranslated-region–coupled luciferase activity and suppressed endogenous SSRP1 expression at both messenger RNA and protein levels. For the first time, we proved that SSRP1 upregulation contributed to HCC development and the tumor-suppressive miR-497 served as its negative regulator.