Feng Xingjun, Miao Guozhuan, Han Yipeng, Xu Yi
Department of Neurosurgery, General Hospital of Chinese People's Armed Police Forces, Beijing, 100039, China,
Tumour Biol. 2014 Jan;35(1):149-54. doi: 10.1007/s13277-013-1018-2. Epub 2013 Jul 27.
Caspase recruitment domain-containing membrane-associated guanylate kinase protein 10 or CARMA3 (CARD10) is a recently characterized oncoprotein involved in the progression of several human malignancies. The present study aims to investigate the expression pattern and biological roles of CARMA3 protein in human glioma. CARMA3 expression was analyzed in 97 glioma specimens using immunohistochemistry. We observed negative staining in normal astrocytes and positive staining of CARMA3 in 25 out of 97 (25.8%) glioma samples. Overexpression of CARMA3 correlated with tumor grade (p < 0.001). Small interfering RNA knockdown was performed in A172 cell line with relatively high CARMA3 expression. Using colony formation assay and Matrigel invasion assay, we showed that CARMA3 depletion in A172 cell line inhibited cell proliferation and cell invasion. In addition, mRNA and protein levels of matrix metallopeptidase 9 (MMP9) were downregulated, indicating CARMA3 might regulate invasion through MMP9. In conclusion, CARMA3 serves as an oncoprotein in human glioma by regulating cell invasion, possibly through MMP9 regulation.
含半胱天冬酶招募结构域的膜相关鸟苷酸激酶蛋白10或CARMA3(CARD10)是一种最近被鉴定的癌蛋白,参与多种人类恶性肿瘤的进展。本研究旨在探讨CARMA3蛋白在人类胶质瘤中的表达模式及生物学作用。采用免疫组织化学方法分析了97例胶质瘤标本中CARMA3的表达情况。我们观察到正常星形胶质细胞呈阴性染色,97例胶质瘤样本中有25例(25.8%)CARMA3呈阳性染色。CARMA3的过表达与肿瘤分级相关(p<0.001)。在CARMA3表达相对较高的A172细胞系中进行小干扰RNA敲低实验。通过集落形成实验和基质胶侵袭实验,我们发现A172细胞系中CARMA3的缺失抑制了细胞增殖和细胞侵袭。此外,基质金属蛋白酶9(MMP9)的mRNA和蛋白水平下调,表明CARMA3可能通过MMP9调节侵袭。总之,CARMA3可能通过调节MMP9,调控细胞侵袭,从而在人类胶质瘤中发挥癌蛋白的作用。