Abstract
At present, colorectal cancer (CRC) has become a serious threat to human health in the world. Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent hydrolase that may be involved in several physiological processes. However, whether DPP3 affects the development and progression of CRC remains a mystery. This study is the first to demonstrate the role of DPP3 in CRC. Firstly, the results of immunohistochemistry analysis showed the upregulation of DPP3 in CRC tissues compared with normal tissues, which is statistically analyzed to be positively correlated with lymphatic metastasis, pathological stage, positive number of lymph nodes. Moreover, the high expression of DPP3 predicts poor prognosis in CRC patients. In addition, the results of cell dysfunction experiments clarified that the downregulation of DPP3 significantly inhibited cell proliferation, colony formation, cell migration, and promoted apoptosis in vitro. DPP3 depletion could induce cell apoptosis by upregulating the expression of BID, BIM, Caspase3, Caspase8, HSP60, p21, p27, p53, and SMAC. In addition, downregulation of DPP3 can reduce tumorigenicity of CRC cells in vivo. Furthermore, CDK1 is determined to be a downstream target of DPP3-mediated regulation of CRC by RNA-seq, qPCR, and WB. The interaction between DPP3 and CDK1 shows mutual regulation. Specifically, downregulation of DPP3 can accentuate the effects of CDK1 knockdown on the function of CRC cells. Overexpression of CDK1 alleviates the inhibitory effects of DPP3 knockdown in CRC cells. In summary, DPP3 has oncogene-like functions in the development and progression of CRC by targeting CDK1, which may be an effective molecular target for the prognosis and treatment of CRC.
Highlights
Colorectal cancer (CRC) is the result of the gradual accumulation of a series of genetic and epigenetic changes in normal colonic epithelial cells, contributing to colorectal adenomas and invasive adenocarcinomas[1]
The high expression of dipeptidyl peptidase 3 (DPP3) in CRC is significantly correlated with poor prognosis
This result was further verified by Spearman rank correlation analysis, indicating that the increased expression of DPP3 is a warning of deterioration in patients with CRC (Table 3)
Summary
Colorectal cancer (CRC) is the result of the gradual accumulation of a series of genetic and epigenetic changes in normal colonic epithelial cells, contributing to colorectal adenomas and invasive adenocarcinomas[1]. It is one of the leading causes of cancer-related death worldwide and has the characteristics of high incidence[2]. Human DPP3, a 29,647 bp gene (NC_000011.10), located on chromosome 11q12-13.113. The primary biological function of DPP3 is to regulate the transformation of enkephalin, opioid peptide, terminal protein, and cell signaling[11]. Little information is available on the expression, specificity, and function of DPP3 in human cancers
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