Ao Ning, Liu Yanyan, Bian Xiaocui, Feng Hailiang, Liu Yuqin
Department of Pathology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, Beijing 100005, P.R. China.
Mol Med Rep. 2015 Aug;12(2):2107-13. doi: 10.3892/mmr.2015.3661. Epub 2015 Apr 22.
Colon cancer is associated with increased cell migration and invasion. In the present study, the role of ubiquitin-specific peptidase 22 (USP22) in signal transducer and activator of transcription 3 (STAT3)-mediated colon cancer cell invasion was investigated. The messenger RNA levels of STAT3 target genes were measured by reverse transcription-quantitative polymerase chain reaction, following USP22 knockdown by RNA interference in SW480 colon cancer cells. The matrix metalloproteinase 9 (MMP9) proteolytic activity and invasion potential of SW480 cells were measured by zymography and Transwell assay, respectively, following combined USP22 and STAT3 short interfering (si)RNA treatment or STAT3 siRNA treatment alone. Similarly, a cell counting kit-8 assay was used to detect the proliferation potential of SW480 cells. The protein expression levels of USP22, STAT3 and MMP9 were detected by immunohistochemistry in colon cancer tissue microarrays (TMAs) and the correlation between USP22, STAT3 and MMP9 was analyzed. USP22/STAT3 co-depletion partly rescued the MMP9 proteolytic activity and invasion of SW480 cells, compared with that of STAT3 depletion alone. However, the proliferation of USP22/STAT3si-SW480 cells was decreased compared with that of STAT3si-SW480 cells. USP22 expression was positively correlated with STAT3 and MMP9 expression in colon cancer TMAs. In conclusion, USP22 attenuated the invasion capacity of colon cancer cells by inhibiting the STAT3/MMP9 signaling pathway.
结肠癌与细胞迁移和侵袭增加有关。在本研究中，研究了泛素特异性肽酶22（USP22）在信号转导和转录激活因子3（STAT3）介导的结肠癌细胞侵袭中的作用。在SW480结肠癌细胞中通过RNA干扰敲低USP22后，通过逆转录-定量聚合酶链反应测量STAT3靶基因的信使RNA水平。在联合使用USP22和STAT3小干扰（si）RNA处理或单独使用STAT3 siRNA处理后，分别通过酶谱分析和Transwell试验测量SW480细胞的基质金属蛋白酶9（MMP9）蛋白水解活性和侵袭潜力。同样，使用细胞计数试剂盒8试验检测SW480细胞的增殖潜力。通过免疫组织化学在结肠癌组织微阵列（TMA）中检测USP22、STAT3和MMP9的蛋白表达水平，并分析USP22、STAT3和MMP9之间的相关性。与单独敲低STAT3相比，USP22/STAT3共同缺失部分挽救了SW480细胞的MMP9蛋白水解活性和侵袭能力。然而，与STAT3si-SW480细胞相比，USP22/STAT3si-SW480细胞的增殖减少。在结肠癌TMA中，USP22表达与STAT3和MMP9表达呈正相关。总之，USP22通过抑制STAT/MMP9信号通路减弱结肠癌细胞的侵袭能力。
