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CIP2A is overexpressed in human endometrioid adenocarcinoma and regulates cell proliferation,invasion and apoptosis
Authors:Ning Yu  TingGuo Zhang  DaHua Zhao  Zhang Cao  Jing Du  Qian Zhang
Affiliation:1. Department of Pathology, Shandong University School of Medicine, JiNan 250012, China;2. Department of Pathology, Affiliated Hospital of BinZhou Medical University, BinZhou 256604, China;3. Department of Pathology, BinZhou Medical University, YanTai 264003, China;4. Center of Cancer Research, Affiliated Hospital of BinZhou Medical University, BinZhou 256604, China
Abstract:

Objective

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein that stabilizes c-Myc and promotes cell proliferation and transformation. Here, we investigated the clinical significance and biological function of CIP2A in endometrial cancer.

Method

CIP2A expression was assessed in normal endometrium, endometrial hyperplasia, endometrial atypical hyperplasia, and endometrioid adenocarcinoma tissues using immunohistochemistry, western blot, and RT-PCR. The effect of reduced CIP2A expression was assessed by siRNA knockdown in Ishikawa and An3ca endometrial cell lines. The roles of CIP2A in proliferation, apoptosis, and the cell cycle were assessed using CCK-8 assays, colony formation assays, and flow cytometry, respectively.

Results

Our results show that CIP2A expression was higher in endometrioid adenocarcinoma tissues and cell lines. Furthermore, CIP2A siRNA significantly reduced the proliferation rate and invasion of Ishikawa and An3ca cells, and induced a significant level of apoptosis in Ishikawa cells. Moreover, CIP2A depletion resulted in reduced c-Myc and cyclin D1 protein levels, and increased caspase-3 expression.

Conclusions

CIP2A is overexpressed in endometrioid adenocarcinoma and CIP2A promotes the malignant growth and invasion,decrease apoptosis in entometrioid adenocarcinoma cell lines. These results validate that CIP2A plays an important role in the carcinogenesis of endometrioid adenocarcinoma and establishes CIP2A as a clinically relevant oncoprotein and may presents a promising therapeutic target for cancer treatment.
Keywords:CIP2A  Endometrioid adenocarcinoma  Apoptosis  Proliferation  Invasion
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