PADI3 plays an antitumor role via the Hsp90/CKS1 pathway in colon cancer

Zhengbin Chai,Tingting Zhu,Chunyan Liu,Yabing Zheng,Yingying Zheng,Zhiwei Zhang,Na Liang,Xiwei Wang,Chuanxi Zhao,Li Wang

doi:10.1186/s12935-019-0999-3

Abstract

BackgroundCKS1 is highly expressed in colon cancer tissues, and is essential for cancer cell proliferation. The downstream molecular mechanism of CKS1 has been fully studied, but the upstream regulatory mechanism of it is still unclear. Earlier research found that PADI3 plays its anti-tumor roles via suppress cell proliferation, in this study, we found that the expression pattern of PADI3 and CKS1 are negatively correlated in colon cancer tissues, and overexpression of PADI3 can partly reverse CKS1 induced cancer cell proliferation. However, the regulatory mechanism of PADI3 and CKS1 in the tumorigenesis of colon cancer is still unclear and need to do further research.MethodsWestern blot and real-time PCR were used to detect the expression levels of genes. CCK-8 and colony formation assays were used to examine cell proliferation and colony formation ability. Overexpression and rescue experiments were used to study the molecular mechanism of CKS1 in colon cancer cells, BALB/c nude mice were used to study the function of CKS1 in vivo.ResultsCKS1 is highly expressed in colon cancer tissues, and the overexpression of CKS1 promotes cell proliferation and colony formation in both HCT116 (originating from primary colon cancer) and SW620 (originating from metastatic tumor nodules of colon cancer) cells. CKS1-expressing HCT116 cells produced larger tumors than the control cells. The expression pattern of PADI3 and CKS1 are negatively correlation in clinical samples of colon cancer, further study indicates that PADI3 can significantly decrease Hsp90 and CKS1 expression, and Hsp90 is essential for PADI3 to downregulate CKS1expression in colon cancer cells.ConclusionsPADI3 exerts its antitumor activity by inhibiting Hsp90 and CKS1 expression, and Hsp90 is essential for PADI3 to suppress CKS1 expression.

Highlights

CKS1 is highly expressed in colon cancer tissues, and is essential for cancer cell proliferation
CKS1 is highly expressed in colon cancer tissues To fully study the function of CKS1 in colon cancer, the expression profile of it was examined using western blot and qRT-PCR in colon cancer tissues and their corresponding adjacent tissues which were obtained from 12 different patients
CKS1 promotes colon cancer cell proliferation and colony formation To investigate the role of CKS1 in colon cancer, CKS1 was transfected into HCT116 cells and SW620 cells to study the proliferation ratio and colony formation activity

Summary

Introduction

CKS1 is highly expressed in colon cancer tissues, and is essential for cancer cell proliferation. Earlier research found that PADI3 plays its anti-tumor roles via suppress cell proliferation, in this study, we found that the expression pattern of PADI3 and CKS1 are negatively correlated in colon cancer tissues, and overexpression of PADI3 can partly reverse CKS1 induced cancer cell proliferation. The loss of cell cycle control is one of the major causes of tumorigenesis, further studies on the Cyclin-dependent kinase regulatory subunits (CKSs) can interact with Cyclin-dependent kinases (CDKs) to regulate the cell cycle [3]. Increasing evidences have shown that CKS1 has high expression level in various cancers, such as colorectal carcinoma, lung cancer, prostate carcinoma, breast cancer, lymphomas and take part in tumorigenesis as an oncogene [6,7,8,9,10]. The inhibition of CKS1 expression is important for cell cycle control in tumor cells, and it

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