Open AccessOverexpression of CIP2A is associated with poor prognosis in multiple myeloma
Author(s) -
Xuewen Li,
Wei Cao,
Shanshan Qin,
Te Zhang,
Junnian Zheng,
Ying Dong,
Pinghong Ming,
Cheng Qian,
Zheng Lu,
Yang Guo,
Baofu Zhang,
Ying Li
Publication year - 2017
Publication title -
signal transduction and targeted therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.284
H-Index - 33
eISSN - 2095-9907
pISSN - 2059-3635
DOI - 10.1038/sigtrans.2017.13
Subject(s) - protein phosphatase 2 , multiple myeloma , carcinogenesis , cancer research , bone marrow , protein kinase b , tumor progression , gene knockdown , medicine , in vivo , cell growth , cancer , biology , phosphatase , cell culture , immunology , phosphorylation , microbiology and biotechnology , genetics
Cancerous inhibitor of protein phosphatase 2A (CIP2A), an endogenous protein phosphatase 2A (PP2A) inhibitor, has been identified as an oncoprotein in promoting cancer initiation and progression of several types of cancer. However, the expression and the role played by CIP2A in the pathogenesis of multiple myeloma (MM) remain unclear. In this study, we showed that CIP2A was overexpressed in human MM cell lines and MM patients’ bone marrow tissues. Clinicopathologic analysis showed that CIP2A expression was significantly correlated with clinical stage and percent of plasma cells in bone marrow. Kaplan–Meier analysis revealed that patients with high CIP2A expression presented with poorer overall survival rates than those with low CIP2A expression. Moreover, CIP2A knockdown in MM cells resulted in attenuated proliferative abilities. In addition, CIP2A depletion sensitizes dexamethasone (Dex)-resistant cells to Dex. The effect of CIP2A on proliferation and Dex therapy was mediated by the inhibition of PP2A, which in turn activated Akt. In vivo studies confirmed that CIP2A regulated MM tumorigenesis and the phosphorylation of Akt. Taken together, our results suggest that CIP2A oncoprotein plays an important role in MM progression and could serve as a prognosis marker and a novel therapeutic target for the treatment of patients with MM.