DPP3/CDK1 contributes to the progression of colorectal cancer through regulating cell proliferation, cell apoptosis, and cell migration

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.

Identification of an Endoplasmic Reticulum Stress-Related Gene Signature to Evaluate the Immune Status and Predict the Prognosis of Hepatocellular Carcinoma

“…CDK1 belongs to cyclin-dependent kinase family and participates in regulating the G2/M phase transition during the cell cycle ( Malumbres, 2014 ). CDK1 was overexpressed in colorectal cancer and liver cancer and can promote cell proliferation and induce apoptosis ( Tong et al, 2021 ). These previous studies indicated that the six ERGs played crucial roles in cancer progression, which provided some basic support for our research.…”

[Retracted] Identification of Hub Genes for Early Diagnosis and Predicting Prognosis in Colon Adenocarcinoma

“…CDK1 plays a key role in the regulation of eukaryotic cell cycle and is essential for G1/S and G2/M transition of eukaryotic cell cycle [ 61 ]. Many biological experiments have demonstrated that CDK1 is highly expressed in colon cancer cells [ 62 , 63 ] and participates in apoptosis. CDK1 may act as a potential diagnostic and therapeutic target in view of its extensive involvement in the regulation of colorectal cancer development and progression [ 62 ].…”

Transcriptome Profiling of HCT-116 Colorectal Cancer Cells with RNA Sequencing Reveals Novel Targets for Polyphenol Nano Curcumin

“…According to the gene-pathway annotated network, it is revealed that CDK1 is involved in the cell cycle and associated with other CRC-related genes (CCNA2, BUB1B, GADD45G, ATF3). CDK1 contributes to the cell proliferation, apoptosis, and cell migration [ 20 , 21 ]. It was shown that the upregulation of CDK1 leads to poor prognosis in patients with CRC [ 22 ].…”