The novel miR-1269b-regulated protein SVEP1 induces hepatocellular carcinoma proliferation and metastasis likely through the PI3K/Akt pathway
The novel miR-1269b-regulated protein SVEP1 induces hepatocellular carcinoma proliferation and metastasis likely through the PI3K/Akt pathway
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新型 miR-1269b 调节蛋白 SVEP1 可能通过 PI3K/Akt 通路诱导肝细胞癌增殖和转移
DOI：
10.1038/s41419-020-2535-8
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发表时间：
2020-05-05
影响因子：
9
通讯作者：
Zhang, Ti
中科院分区：
文献类型：
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作者：
Chen, Lu;Liu, Dongming;Zhang, Ti
细胞间粘附减少是许多癌症（包括肝细胞癌（HCC））转移和复发的关键步骤。SVEP 1是一种重要的细胞粘附分子，在调节细胞间粘附和胚胎淋巴管发育中起关键作用。然而，SVEP 1在HCC中的表达模式和作用在很大程度上仍然未知。我们通过分析来自我们癌症中心的220个HCC样本来鉴定SVEP 1表达。TCGA和GEO在线数据库用于数据校准和验证。SVEP 1在两组复发风险不同的HCC中差异表达，被认为是HCC预后的独立危险因素。SVEP 1的表达与HCC的增殖和转移呈负相关。SVEP 1表达下调促进体外HCC细胞迁移、趋化性、侵袭和增殖，以及小鼠模型中的体内肿瘤生长、局部侵袭和转移。生物信息学分析和RT-PCR结果显示，miR-1269 b的表达与SVEP 1的表达及HCC患者的预后呈负相关。进一步的实验表明，miR-1269 b直接靶向并下调SVEP 1的表达，这进一步诱导Akt在thr 308处的磷酸化。这些调节作用最终介导HCC细胞的增殖和转移。SVEP 1可作为HCC的一个有希望的预后标志物。miR-1269 b下调SVEP 1表达并促进HCC增殖和转移可能通过PI 3 k/Akt信号通路。
Decreased intercellular adhesion is a key step in the metastasis and recurrence of many cancers, including hepatocellular carcinoma (HCC). SVEP1 is an important cell adhesion molecule that plays a key role in regulating intercellular adhesion and embryonic lymphatic development. However, the expression patterns and roles of SVEP1 in HCC are still largely unknown. We identified SVEP1 expression by analyzing 220 HCC samples from our cancer center. TCGA and GEO online-databases were used for data calibration and validation. SVEP1 was differentially expressed in two groups of HCCs with different risks of recurrence and was deemed as an independent risk factor for the prognosis of HCC. The expression of SVEP1 is negatively related to the proliferation and metastasis of HCC. Downregulation of SVEP1 expression promoted in vitro HCC cell migration, chemotaxis, invasion and proliferation, as well as in vivo tumor growth, local invasion and metastasis in a mouse model. Bioinformatic analysis and RT-PCR results showed that miR-1269b expression is negatively correlated with the SVEP1 expression and the prognosis of HCC patients. Further experiments showed that miR-1269b directly targets and downregulates the expression of SVEP1, which further induces the phosphorylation of Akt at thr308. These regulatory effects ultimately mediate the proliferation and metastasis of HCC cells. SVEP1 could serve as a promising prognostic marker of HCC. MiR-1269b downregulates SVEP1 expression and promotes HCC proliferation and metastasis likely through the PI3k/Akt signaling pathway.