miR-27a Downregulation Promotes Cutaneous Squamous Cell Carcinoma Progression via Targeting EGFR
miR-27a Downregulation Promotes Cutaneous Squamous Cell Carcinoma Progression via Targeting EGFR
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miR-27a 下调通过靶向 EGFR 促进皮肤鳞状细胞癌进展
DOI：
10.3389/fonc.2019.01565
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发表时间：
2020-01-21
影响因子：
4.7
通讯作者：
Zhou, Meijuan
中科院分区：
文献类型：
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作者：
Wang, Yinghui;Deng, Xuyi;Zhou, Meijuan
皮肤鳞状细胞癌（Cutaneous squamous cell carcinoma，cSCC）是世界范围内第二常见的恶性肿瘤，其病因与紫外线辐射有关。miRNA在癌症的发生和发展中起着重要作用。然而，miRNAs在cSCC中的功能仍有待阐明。在这里，我们筛选并鉴定了miR-27 a作为HaCaT细胞中UVB照射后持续下调的miRNA。发现miR-27 a在cSCC细胞和组织中的表达显著降低。体内外实验表明，miR-27 a抑制cSCC细胞的增殖和侵袭。从机制上讲，EGFR被miR-27 a直接靶向，miR-27 a抑制EGFR的磷酸化及其下游NF-κB信号通路。总体而言，这些发现表明，下调miR-27 a通过靶向EGFR及其下游NF-κB信号通路促进肿瘤生长和转移，提示miR-27 a在cSCC的进展中起着至关重要的作用，并可能成为新的治疗靶点。
Cutaneous squamous cell carcinoma (cSCC) is the second common malignant cancer around the worldwide and is etiologically linked to ultraviolet radiation. miRNAs play an important role in the initiation and progression of cancers. However, the functions of miRNAs in cSCC remain to be elucidated. Here, we screened and identified miR-27a as a consistently downregulated miRNA after UVB irradiation in HaCaT cells. It was found that miR-27a expression was significantly decreased in cSCC cells and tissues. in vitro and in vivo experiments showed that miR-27a inhibited cell proliferation and invasion of cSCC cells. Mechanistically, EGFR was identified to be directly targeted by miR-27a and miR-27a suppressed the phosphorylation of EGFR and its downstream NF-κB signaling pathway. Overall, these findings suggest that downregulation of miR-27a promotes tumor growth and metastasis via targeting EGFR and its downstream NF-κB signaling pathway, reminding that miR-27a plays a vital role in the progression of cSCC and could be a new therapeutic target.