Zhai Mo, Cong Lin, Han Yaxin, Tu Guanjun
Department of Orthopaedics, The First Hospital of China Medical University, No. 155 Nanjingbei Street, Heping District, Shenyang, 110001, China.
Tumour Biol. 2014 Feb;35(2):1123-8. doi: 10.1007/s13277-013-1150-z. Epub 2013 Sep 8.
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a newly characterized oncoprotein involved in a variety of malignant tumors. However, its expression pattern and biological functions in osteosarcoma remain unclear. In the present study, CIP2A expression was analyzed in 51 human osteosarcoma specimens using immunohistochemistry. CIP2A siRNA was used in the MG-63 cell line, and the effect of CIP2A depletion on cell proliferation and invasion was evaluated. We found that CIP2A was overexpressed in 76.5 % (39/51) of osteosarcoma tissues, while normal bone tissues showed negative CIP2A expression. In addition, the positive rate of CIP2A expression was higher in stage IIB osteosarcoma than stage IIA cases. Knockdown of the CIP2A expression significantly reduced osteosarcoma cell proliferation and invasion, with decreased c-Myc expression and p-AKT expression. CIP2A depletion also facilitated apoptosis and inhibited MMP9 mRNA expression. Taken together, our data identified CIP2A as a critical oncoprotein involved in cell proliferation and invasion, which could serve as a therapeutic target in osteosarcoma.
蛋白磷酸酶2A的癌性抑制剂(CIP2A)是一种新发现的参与多种恶性肿瘤的癌蛋白。然而,其在骨肉瘤中的表达模式和生物学功能仍不清楚。在本研究中,采用免疫组织化学方法分析了51例人类骨肉瘤标本中CIP2A的表达情况。在MG-63细胞系中使用CIP2A siRNA,并评估CIP2A缺失对细胞增殖和侵袭的影响。我们发现,76.5%(39/51)的骨肉瘤组织中CIP2A过表达,而正常骨组织中CIP2A表达为阴性。此外,IIB期骨肉瘤中CIP2A表达的阳性率高于IIA期病例。敲低CIP2A表达可显著降低骨肉瘤细胞的增殖和侵袭,同时c-Myc表达和p-AKT表达降低。CIP2A缺失还促进了细胞凋亡并抑制了MMP9 mRNA表达。综上所述,我们的数据确定CIP2A是一种参与细胞增殖和侵袭的关键癌蛋白,可作为骨肉瘤的治疗靶点。