TGF-ß regulates the ERK/MAPK pathway independent of the SMAD pathway by repressing miRNA-124 to increase MALAT1 expression in nasopharyngeal carcinoma
TGF-ß regulates the ERK/MAPK pathway independent of the SMAD pathway by repressing miRNA-124 to increase MALAT1 expression in nasopharyngeal carcinoma
复制标题
TGF-ss通过抑制miRNA-124来独立于SMAD通路调节ERK/MAPK通路以增加鼻咽癌中MALAT1的表达
DOI：
10.1016/j.biopha.2018.01.120
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发表时间：
2018-03-01
影响因子：
7.5
通讯作者：
Yin, Li
中科院分区：
文献类型：
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作者：
Du, Mingyu;Chen, Wei;Yin, Li
转化生长因子β（TGF-β）是一种多效性细胞因子，在包括鼻咽癌（NPC）在内的多种癌症中促进细胞增殖和迁移。microRNA-124（miR-124）在NPC中下调并抑制这种疾病的肿瘤发生。然而，miR-124在TGF-β诱导的NPC发展中的作用仍然未知。在这项研究中，恒定的TGF-β刺激抑制miR-124的表达，而miR-124过表达拮抗TGF-β促进的NPC细胞生长和迁移。miR-124过表达降低了p-SMAD 2/3、SMAD 4和p-ERK水平，表明异位miR-124过表达抑制了SMAD和非SMAD途径。原癌lncRNA MALAT 1被miR-124靶向，miR-124通过靶向MALAT 1独立于SMAD信号通路调节ERK/MAPK。总之，我们的工作阐明了miR-124在TGF-β信号通路中独立于SMAD信号通路的重要作用，并显示了miR-124作为NPC新治疗靶点的潜力。
Transforming growth factor beta (TGF-ss), a pleiotropic cytokine, promotes cell proliferation and migration in multiple cancers, including nasopharyngeal carcinoma (NPC). microRNA-124 (miR-124) becomes downregulated in NPC and inhibits the tumorigenesis of this disease. However, the role of miR-124 in TGF-ss-induced NPC development remains unknown. In this study, constant TGF-ss stimulation repressed miR-124 expression, whereas miR-124 overexpression antagonized TGF-ss-promoted NPC cell growth and migration. miR-124 overexpression decreased p-SMAD2/3, SMAD4, and p-ERK levels, indicating that ectopic miR-124 overexpression inhibited SMAD and non-SMAD pathways. Pro-oncogenic lncRNA MALAT1 was targeted by miR-124 that regulated ERK/MAPK by targeting MALAT1 independent of the SMAD signaling pathway. In conclusion, our work clarified the significant role of miR-124 in TGF-ss signaling pathways independent of the SMAD signaling pathway and showed the potential of miR-124 as a new therapeutic target against NPC.