DPP3/CDK1 contributes to the progression of colorectal cancer through regulating cell proliferation, cell apoptosis, and cell migration.
DPP3/CDK1 contributes to the progression of colorectal cancer through regulating cell proliferation, cell apoptosis, and cell migration.
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DPP3/CDK1 通过调节细胞增殖、细胞凋亡和细胞迁移促进结直肠癌的进展
DOI：
10.1038/s41419-021-03796-4
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发表时间：
2021-05-22
影响因子：
9
通讯作者：
Lai D
中科院分区：
文献类型：
--
作者：
Tong Y;Huang Y;Zhang Y;Zeng X;Yan M;Xia Z;Lai D
目前，结直肠癌已成为严重威胁人类健康的疾病。二肽基肽酶3(DPP3)是一种锌依赖的水解酶，可能参与多种生理过程。然而，DPP3是否影响结直肠癌的发生发展仍是个谜。这项研究首次证明了DPP3在结直肠癌中的作用。首先，免疫组织化学检测结果显示，DPP3在大肠癌组织中的表达较正常组织明显上调，并与淋巴结转移、病理分期、阳性淋巴结数目呈正相关。此外，DPP3的高表达预示着结直肠癌患者预后不良。此外，细胞功能障碍实验结果表明，DPP3的下调在体外显著抑制了细胞的增殖、克隆形成、细胞迁移，促进了细胞的凋亡。DPP3缺失可通过上调Bid、BIM、Caspase3、Caspase8、HSP60、p21、p27、P53和Smac的表达而诱导细胞凋亡。此外，下调DPP3可以降低结直肠癌细胞在体内的致瘤性。此外，CDK1被确定为DPP3介导的RNA-seq、qPCR和WB调节CRC的下游靶点。DPP3和CDK1之间的相互作用是相互调节的。具体地说，下调DPP3可以加重CDK1基因敲除对CRC细胞功能的影响。CDK1过表达可减轻DPP3基因敲除对结直肠癌细胞的抑制作用。综上所述，DPP3通过靶向CDK1在结直肠癌的发生发展过程中发挥癌基因样作用，可能成为判断结直肠癌预后和治疗的有效分子靶点。
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.
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影响因子：
3.7
作者：
Drury LJ;Wendt MK;Dwinell MB
通讯作者：
Dwinell MB
有希望的结直肠癌的新药物。
影响因子：
4.3
作者：
Das S;Ciombor KK;Haraldsdottir S;Goldberg RM
通讯作者：
Goldberg RM
影响因子：
2.3
作者：
Enserink JM;Kolodner RD
通讯作者：
Kolodner RD
影响因子：
4.8
作者：
Hegde, R;Srinivasula, SM;Alnemri, ES
通讯作者：
Alnemri, ES
影响因子：
5.8
作者：
Makin, Guy
通讯作者：
Makin, Guy