The USP22 promotes the growth of cancer cells through the DYRK1A in pancreatic ductal adenocarcinoma
| Autor: | Yang Du, Yong Cheng, Zhile Bai, Lin Cong |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male endocrine system diseases Transplantation Heterologous Mice Nude Apoptosis Biology Protein Serine-Threonine Kinases 03 medical and health sciences Mice 0302 clinical medicine Ubiquitin Cell Line Tumor Genetics medicine Animals Humans RNA Messenger Tyrosine Cell Proliferation Gene knockdown Mice Inbred BALB C Cell growth Kinase Pancreatic Ducts Cancer General Medicine Oncogenes Protein-Tyrosine Kinases medicine.disease digestive system diseases Gene Expression Regulation Neoplastic Pancreatic Neoplasms 030104 developmental biology Cell culture 030220 oncology & carcinogenesis Cancer cell biology.protein Cancer research Ubiquitin Thiolesterase Neoplasm Transplantation Carcinoma Pancreatic Ductal |
| Zdroj: | Gene. 758 |
| ISSN: | 1879-0038 |
| Popis: | As a member of the ubiquitin-specific protease (USP) family, USP22 could remove ubiquitin moieties from its target proteins to control the function of the target proteins. Accumulating studies show that USP22 essentially participates in diverse types of cancer as an oncogene-like protein. However, the roles of USP22 in human pancreatic ductal adenocarcinoma (PDAC) and the underlying mechanism are unknown. Here we report that USP22 promotes the growth of PDAC cells by promoting the expression of dual-specificity tyrosine regulated kinase 1A (DYRK1A). Our results showed that the expression levels of USP22 were up-regulated in human PDAC tissues and cell lines (BxPC-3, AsPC-1, MIA-PaCa-2, PANC-1, and CAPAN-1). Lentivirus-mediated knockdown of USP22 repressed the rate of proliferation and capacity of colony formation of BxPC3 and CAPAN1 cancer cells and USP22 overexpression promoted the proliferation and capacity of the colony formation of BxPC3 and CAPAN1 cancer cells. The further mechanism study showed that USP22 elevated the expression of the mRNA and protein levels of DYRK1A in PDAC cancer cells. Inhibition of DYRK1A with EHT-5732 or lentivirus-mediated knockdown of DYRK1A blocked the function of USP22 overexpression in the regulation of the proliferation and colony formation of PDAC cells. Taken together, our findings demonstrated that USP22 overexpression in PDAC promoted the growth of the cancer cells partially through upregulating the expression of DYRK1A. |
| Databáze: | OpenAIRE |
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