TRIM14 promotes the migration and invasion of gastric cancer by regulating epithelial‑to‑mesenchymal transition via activation of AKT signaling regulated by miR‑195‑5p.
TRIM14 promotes the migration and invasion of gastric cancer by regulating epithelial‑to‑mesenchymal transition via activation of AKT signaling regulated by miR‑195‑5p.
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DOI：
10.3892/or.2018.6750
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发表时间：
2018-12
期刊：
影响因子：
4.2
通讯作者：
Wei W
中科院分区：
文献类型：
--
作者：
Wang F;Ruan L;Yang J;Zhao Q;Wei W
TRIM 14是TRIM蛋白家族的成员之一，它参与了几个关键的过程，并且在人类癌症中以癌症特异性趋势失调。然而，其在人胃癌（GC）中的表达和功能仍然很大程度上未知。在这项研究中，我们首次证实了TRIM 14 mRNA和蛋白在GC组织和细胞系中上调，如通过qRT-PCR和蛋白质印迹分析所确定的。临床资料显示TRIM 14高表达与肿瘤的侵袭性预后特征，包括晚期TNM分期和淋巴结转移显著相关。在5年生存率方面，TRIM 14可作为胃癌的潜在预后指标。值得注意的是，TRIM 14促进了体外和体内的迁移、侵袭（通过Transwell测量）和上皮至间充质转化（EMT）（通过蛋白质印迹分析和免疫荧光（IF）确定）。此外，TRIM 14诱导蛋白激酶B（AKT）通路激活，抑制AKT逆转了TRIM 14诱导的细胞迁移、侵袭和EMT进展的促进作用。此外，我们证明了TRIM 14的表达受miR-195- 5 p的调控。miR-195- 5 p对胃癌细胞的迁移和侵袭具有抑制作用。最后，我们证实TRIM 14表达的改变消除了miR-195- 5 p对GC细胞的影响。总之，我们的研究结果表明，TRIM 14作为癌基因通过激活AKT信号传导来调节EMT和GC转移，该AKT信号传导由miR-195- 5 p调节，支持其作为GC治疗靶点的潜在效用。
Tripartite motif-containing 14 (TRIM14) is a member of the TRIM protein family which has been implicated in several critical processes and is dysregulated in human cancers in a cancer-specific trend. However, its expression and function in human gastric cancer (GC) are still largely unknown. In this study, we confirmed for the first time that TRIM14 mRNA and protein were upregulated in GC tissues and cell lines as determined by qRT-PCR and western blot analysis. Clinical data disclosed that high TRIM14 expression was significantly associated with aggressive prognostic features, including advanced TNM stage and lymph node metastasis. In regards to 5-year survival, TRIM14 served as a potential prognostic marker for GC. Notably, TRIM14 promoted migration, invasion as measured by Transwell and epithelial-to-mesenchymal transition (EMT) as determined by western blot analysis and immunofluorescence (IF) in vitro and in vivo. Moreover, TRIM14 induced protein kinase B (AKT) pathway activation, and inhibition of AKT reversed the TRIM14-induced promotive effects on cell migration, invasion and EMT progression. Furthermore, we demonstrated that TRIM14 expression was regulated by miR-195-5p. miR-195-5p exerted an inhibitory role in GC migration and invasion. Finally, we confirmed that alteration of TRIM14 expression abolished the effects of miR-195-5p on GC cells. Conclusively, our results demonstrated that TRIM14 functions as an oncogene in regulating EMT and metastasis of GC via activating AKT signaling, which was regulated by miR-195-5p, supporting its potential utility as a therapeutic target for GC.
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