NOD-like receptor X1 functions as a tumor suppressor by inhibiting epithelial-mesenchymal transition and inducing aging in hepatocellular carcinoma cells.
NOD-like receptor X1 functions as a tumor suppressor by inhibiting epithelial-mesenchymal transition and inducing aging in hepatocellular carcinoma cells.
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NOD样受体X1通过抑制肝细胞癌细胞上皮间质转化和诱导衰老发挥抑癌作用
DOI：
10.1186/s13045-018-0573-9
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发表时间：
2018-02-26
影响因子：
28.5
通讯作者：
Huang C
中科院分区：
文献类型：
--
作者：
Hu B;Ding GY;Fu PY;Zhu XD;Ji Y;Shi GM;Shen YH;Cai JB;Yang Z;Zhou J;Fan J;Sun HC;Kuang M;Huang C
本研究旨在探讨核苷酸结合寡聚化结构域（NOD）样受体X1（NLRX 1）在肝细胞癌（HCC）发生发展中的作用。采用逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹（WB）检测临床标本和细胞系中NLRX 1的表达水平。进行Transwell测定来评估NLRX 1对细胞侵袭的影响，并使用流式细胞术来评估细胞凋亡。通过WB确定磷酸肌醇3-激酶（PI 3 K）-AKT途径中关键分子的表达模式。用β-半乳糖苷酶测定评价NLRX 1对细胞衰老的影响。Kaplan-Meier分析和考克斯回归模型用于预后评估。与邻近正常肝组织相比，NLRX 1在肿瘤组织中下调。低肿瘤NLRX 1表达被确定为HCC预后的独立指标（复发：风险比[HR] 1.87，95%置信区间[CI] 1.26-2.76，总生存期[OS] 2.26，95% CI 1.44-3.56）。NLRX 1过表达（OE）可显著抑制肝癌细胞的侵袭能力并诱导其凋亡。体内实验表明，NLRX 1敲低（KD）显著促进HCC生长。从机制上讲，NLRX 1通过降低AKT的磷酸化从而下调Snail 1的表达，从而抑制HCC细胞中的上皮间质转化（EMT），从而表现出抑制功能。此外，NLRX 1 OE可通过AKT-P21依赖性方式诱导细胞衰老。NLRX 1通过抑制PI 3 K-AKT信号通路诱导细胞凋亡、促进衰老、降低侵袭力等作用，在HCC中发挥抑癌作用。未来的研究将集中在恢复NLRX 1的表达，为HCC治疗提供新的见解。本文的在线版本（10.1186/s13045-018-0573-9）包含补充材料，可供授权用户使用。
This study was performed to investigate the role of nucleotide-binding oligomerization domain (NOD)-like receptor X1 (NLRX1) in regulating hepatocellular carcinoma (HCC) progression. Expression levels of NLRX1 in clinical specimens and cell lines were determined by reverse transcription-polymerase chain reaction (RT-PCR) and western blot (WB). Transwell assays were conducted to evaluate the effect of NLRX1 on cell invasion, and flow cytometry was used to assess apoptosis. Expression patterns of key molecules in the phosphoinositide 3-kinase (PI3K)-AKT pathways were determined via WB. The effect of NLRX1 on cell senescence was evaluated with β-galactosidase assays. Kaplan-Meier analyses and Cox regression models were used for prognostic evaluation. NLRX1 was downregulated in tumor tissue compared with adjacent normal liver tissue. Low tumor NLRX1 expression was identified as an independent indicator for HCC prognosis (recurrence: hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.26–2.76, overall survival [OS] 2.26, 95% CI 1.44–3.56). NLRX1 over-expression (OE) significantly inhibited invasiveness ability and induced apoptosis in HCC cells. In vivo experiments showed that NLRX1 knock-down (KD) significantly promoted HCC growth. Mechanistically, NLRX1 exhibited a suppressor function by decreasing phosphorylation of AKT and thus downregulating Snail1 expression, which inhibited epithelial-mesenchymal-transition (EMT) in HCC cells. Moreover, NLRX1 OE could induce cell senescence via an AKT-P21-dependent manner. NLRX1 acted as a tumor suppressor in HCC by inducing apoptosis, promoting senescence, and decreasing invasiveness by repressing PI3K-AKT signaling pathway. Future investigations will focus on restoring expression of NLRX1 to provide new insights into HCC treatment. The online version of this article (10.1186/s13045-018-0573-9) contains supplementary material, which is available to authorized users.
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影响因子：
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