The mechanism by which miR‐605‐3p regulates hepatocellular carcinoma (HCC) metastasis has not been clarified. In this study, we found that miR‐605‐3p was down‐regulated in HCC and that low miR‐605‐3p expression was associated with tumour thrombus and tumour satellites. HCC patients with low miR‐605‐3p expression showed shorter overall survival and disease‐free survival after surgery. Overexpression of miR‐605‐3p inhibited epithelial‐mesenchymal transition and metastasis of HCC through NF‐κB signalling by directly inhibiting expression of TRAF6 , while silencing of miR‐605‐3p had the opposite effect. We also found that SNHG16 directly bound to miR‐605‐3p as a competing endogenous RNA. Mechanistically, high expression of SNHG16 promoted binding to miR‐605‐3p and inhibited its activity, which led to up‐regulation of TRAF6 and sustained activation of the NF‐κB pathway, which in turn promoted epithelial‐mesenchymal transition and metastasis of HCC. TRAF6 increased SNHG16 promoter activity by activating NF‐κB, thereby promoting the transcriptional expression of SNHG16 and forming a positive feedback loop that aggravated HCC malignancy. Our findings reveal a mechanism for the sustained activation of the SNHG16 /miR‐605‐3p /TRAF6 /NF‐κB feedback loop in HCC and provide a potential target for a new HCC treatment strategy.

中文翻译：

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SNHG16 / miR-605-3p / TRAF6 /NF-κB反馈回路调节肝细胞癌转移。

miR‐605‐3p调节肝细胞癌（HCC）转移的机制尚未阐明。在这项研究中，我们发现在肝癌中miR‐605‐3p被下调，而miR‐605‐3p的低表达与肿瘤血栓和肿瘤卫星有关。miR‐605‐3p表达低的HCC患者术后总体生存期较短且无疾病生存期。miR-605-3p的过表达通过直接抑制TRAF6的表达，通过NF-κB信号传导抑制了HCC的上皮-间质转化和转移，而miR-605-3p的沉默则相反。我们还发现SNHG16作为竞争性内源RNA直接与miR-605-3p结合。从机制上讲，SNHG16的高表达促进了与miR-605-3p的结合并抑制了其活性，这导致TRAF6上调并持续激活NF-κB通路，进而促进了HCC的上皮-间质转化和转移。TRAF6通过激活NF-κB来增加SNHG16启动子的活性，从而促进SNHG16的转录表达并形成正反馈环，从而加重HCC恶性程度。我们的发现揭示了SNHG16 / miR-605-3p / TRAF6持续激活的机制/NF-κB在HCC中的反馈回路，并为新的HCC治疗策略提供了潜在的靶标。