Protein arginine methyltransferase 5 promotes lung cancer metastasis via the epigenetic regulation of miR-99 family/FGFR3 signaling
Protein arginine methyltransferase 5 promotes lung cancer metastasis via the epigenetic regulation of miR-99 family/FGFR3 signaling
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DOI：
10.1016/j.canlet.2018.04.019
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发表时间：
2018-01-01
期刊：
影响因子：
9.7
通讯作者：
Gu, Zhongping
中科院分区：
文献类型：
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作者：
Jing, Pengyu;Zhao, Nan;Gu, Zhongping
蛋白精氨酸甲基转移酶5 （Protein arginine methyltransferase 5, PRMT5）作为肿瘤启动物，通过催化靶分子内精氨酸残基的对称二甲基化（me2s），调控多种癌症进展，如增殖和凋亡。然而，prmt5介导的肺癌转移的确切作用尚不完全清楚。在这里，我们说明了它在体内和体外肺癌转移中的潜在作用。PRMT5在肺肿瘤中频繁过表达，其表达与肿瘤分期、淋巴转移及预后不良呈正相关。在该模型中，PRMT5通过组蛋白H4R3的对称二甲基化抑制miR-99家族的转录，从而增加FGFR3的表达，进而激活Erk1/2和Akt，导致肺癌细胞生长和转移。此外，PRMT5的缺失通过阻断miR-99家族的组蛋白修饰，在肺癌进展中发挥抗转移作用。总的来说，这项研究为PRMT5/miR-99家族/FGFR3轴在调节肺癌进展中的作用提供了新的见解，并确定了PRMT5是一种有前景的预后生物标志物和治疗靶点。(C) 2018作者。Elsevier B.V.出版
Protein arginine methyltransferase 5 (PRMT5) functions as a tumor initiator to regulate several cancer progressions, such as proliferation and apoptosis, by catalyzing the symmetrical dimethylation (me2s) of arginine residues within targeted molecules. However, the exact role of PRMT5-mediated metastasis in lung cancer is not fully understood. Here, we illustrated its potential effects in lung cancer metastasis in vivo and vitro. PRMT5 was frequently overexpressed in lung tumors, and its expression was positively related to tumor stages, lymphatic metastasis and poor outcome. In this model, PRMT5 repressed the transcription of the miR-99 family by symmetrical dimethylation of histone H4R3, which increased FGFR3 expression and in turn activated Erk1/2 and Akt, leading to cell growth and metastasis in lung cancer. Furthermore, loss of PRMT5 exerted anti-metastasis effects on lung cancer progression by blocking histone-modification of miR-99 family. Overall, this study provides new insights into the PRMT5/miR-99 family/FGFR3 axis in regulating lung cancer progression and identifies PRMT5 as a promising prognostic biomarker and therapeutic target. (C) 2018 The Author(s). Published by Elsevier B.V.