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.

作为泛素特异性蛋白酶（USP）家族的成员，USP22可以从其靶蛋白中去除泛素部分，以控制靶蛋白的功能。越来越多的研究表明，USP22本质上以癌基因样蛋白的形式参与多种癌症。但是，USP22在人胰管腺癌（PDAC）中的作用及其潜在机制尚不清楚。在这里，我们报道USP22通过促进双特异性酪氨酸调节激酶​​1A（DYRK1A）的表达来促进PDAC细胞的生长。我们的结果表明，USP22的表达水平在人PDAC组织和细胞系（BxPC-3，AsPC-1，MIA-PaCa-2，PANC-1和CAPAN-1）中上调。慢病毒介导的敲低USP22抑制了BxPC3和CAPAN1癌细胞的增殖速率和集落形成能力，USP22过表达促进了BxPC3和CAPAN1癌细胞的增殖和集落形成能力。进一步的机制研究表明，USP22可提高PDAC癌细胞中DYRK1A的mRNA和蛋白表达。用EHT-5732抑制DYRK1A或慢病毒介导的DYRK1A敲低可阻止USP22过表达的功能调节PDAC细胞的增殖和集落形成。两者合计，我们的发现表明USP22在PDAC中的过表达通过上调DYRK1A的表达部分地促进了癌细胞的生长。