NCOA5 promotes proliferation, migration and invasion of colorectal cancer cells via activation of PI3K/AKT pathway
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Kailv Sun1,*, Sheng Wang1,*, Jun He1,*, Yufeng Xie2, Yang He3,4, Zhenxin Wang2 and Lei Qin1
1Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
2Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China
3Ministry of Health Key Laboratory of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
4Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
*These authors have contributed equally to this work
Lei Qin, email: firstname.lastname@example.org
Zhenxin Wang, email: email@example.com
Yufeng Xie, email: firstname.lastname@example.org
Keywords: nuclear receptor coactivator 5 (NCOA5); colorectal cancer (CRC); proliferation; metastasis; phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) pathway
Received: October 27, 2016 Accepted: July 25, 2017 Published: November 14, 2017
The nuclear receptor coactivator 5 (NCOA5) displays both coactivator and corepressor functions. Previous studies showed that alteration of NCOA5 participates in carcinogenesis and progression. However, its roles in colorectal cancer (CRC) remain unknown. Herein, we demonstrated that expression of NCOA5 in human CRC tissues was notably higher than that in adjacent tissues, which significantly correlated with clinicopathological features such as length of tumor, regional lymph node staging and cancer staging. Knockdown of NCOA5 markedly suppressed proliferation, migration and invasion of SW620 high malignant CRC cells. Silencing of NCOA5 also inhibited in vivo growth of SW620 CRC subcutaneously xenografted tumors in athymic BALB/c nude mice. Meanwhile, Overexpression of NCOA5 facilitated these processes in SW480 low malignant CRC cells. Furthermore, knockdown of NCOA5 induced cell cycle G1 phase arrest in SW620 cells, whereas overexpression of NCOA5 promoted G1 to S phase transition in SW480 cells. Mechanistic studies revealed that NCOA5 upregulated phospho-protein kinase B (p-PKB/AKT), Cyclin D1 and matrix metalloproteinase 9 (MMP9) as well as downregulated P27 in CRC cells. Notably, PI3K inhibitor LY294002 obviously attenuated the effects of NCOA5 on p-AKT, Cyclin D1, P27 and MMP9. Moreover, LY294002 and knockdown of Cyclin D1 or MMP9 remarkably blocked the tumor-promoting activity of NCOA5. Collectively, NCOA5 promoted CRC cell proliferation, migration and invasion by upregulating Cyclin D1 and MMP9 while downregulating P27 to a great extent via activating PI3K/AKT signaling pathway. These findings suggested that NCOA5 exhibits an oncogenic effect in human CRC and represents a novel therapeutic target for CRC.
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