Luo Quan, Li Wei, Zhao Tian, Tian Xin, Liu Yumei, Zhang Xibao
Department of Dermatology, Guangzhou Institute of Dermatology, Guangzhou, China.
Department of Dermatology, Guangzhou Institute of Dermatology, Guangzhou, China.
Arch Biochem Biophys. 2015 Oct 1;583:47-54. doi: 10.1016/j.abb.2015.07.022. Epub 2015 Aug 5.
Dysregulation of miRNAs is a common feature in human cancers, but there are lack of studies on roles of miRNAs in cutaneous squamous cell carcinoma (CSCC). miR-148a, a member of the miR-148/152 family, has been found to be downregulated in different types of cancer and its role in CSCC remains unknown. The study was aimed to investigate the expression and cellular function of miR-148a in CSCC. We found that miR-148a was underexpressed in CSCC tissues and cell lines. MAP3K2, MAP3K4 and MAP3K9 were predicted as the target genes of miR-148a and the latter two genes were verified as the target genes of miR-148a in CSCC cells. Importantly, we demonstrated that the overexpression of miR-148a significantly inhibited CSCC cell proliferation and metastasis via down-regulation of MAP3K9 and MAP3K4 expression. MAP3K4 and MAP3K9 were negatively associated with the expression of miR-148a in CSCC tissues. Our results suggested indicated that miR-148a acts as a tumor suppressor of CSCC via inhibiting MAPK pathway. These results may provide a promising alterative strategy for CSCC therapy.
微小RNA（miRNA）失调是人类癌症的一个常见特征，但关于miRNA在皮肤鳞状细胞癌（CSCC）中的作用研究较少。miR-148a是miR-148/152家族的成员，已发现在不同类型的癌症中其表达下调，而其在CSCC中的作用仍不清楚。本研究旨在探讨miR-148a在CSCC中的表达及细胞功能。我们发现miR-148a在CSCC组织和细胞系中表达不足。丝裂原活化蛋白激酶激酶激酶2（MAP3K2）、丝裂原活化蛋白激酶激酶激酶4（MAP3K4）和丝裂原活化蛋白激酶激酶激酶9（MAP3K9）被预测为miR-148a的靶基因，后两个基因在CSCC细胞中被验证为miR-148a的靶基因。重要的是，我们证明miR-148a的过表达通过下调MAP3K9和MAP3K4的表达显著抑制CSCC细胞增殖和转移。MAP3K4和MAP3K9与CSCC组织中miR-148a的表达呈负相关。我们的结果表明，miR-148a通过抑制丝裂原活化蛋白激酶（MAPK）途径作为CSCC的肿瘤抑制因子。这些结果可能为CSCC治疗提供一种有前景的替代策略。
