OncoTargets and Therapy (Aug 2020)

USP19 Enhances MMP2/MMP9-Mediated Tumorigenesis in Gastric Cancer

  • Dong Z,
  • Guo S,
  • Wang Y,
  • Zhang J,
  • Luo H,
  • Zheng G,
  • Yang D,
  • Zhang T,
  • Yan L,
  • Song L,
  • Liu K,
  • Sun Z,
  • Meng X,
  • Zheng Z,
  • Zhang J,
  • Zhao Y

Journal volume & issue
Vol. Volume 13
pp. 8495 – 8510

Abstract

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Zhe Dong,1,* Shuai Guo,1,* Yue Wang,2 Jun Zhang,2 Haojie Luo,1 Guoliang Zheng,2 Dong Yang,2 Tao Zhang,2 Liucun Yan,3 Li Song,3 Kejia Liu,3 Zhe Sun,3 Xiangyu Meng,2 Zhichao Zheng,2 Jianjun Zhang,2 Yan Zhao2 1Postgraduate School of China Medical University, Shenyang 110001, Liaoning Province, People’s Republic of China; 2Department of Stomach Surgery, Cancer Hospital of China Medical University (Liaoning Cancer Hospital and Institute), Shenyang 110042, Liaoning Province, People’s Republic of China; 3Yidu Cloud (Beijing) Technology Co., Ltd., Beijing 100083, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan ZhaoSurgeon, Department of Stomach Surgery, Cancer Hospital of China Medical University (Liaoning Cancer Hospital and Institute), No. 44 Xiaoheyan Road, Dadong District, Shenyang 110042, Liaoning Province, People’s Republic of ChinaTel +86-24-31916622Fax +86-24-24315679Email [email protected]: To investigate the clinical significance of ubiquitin-specific peptidase 19 (USP19) expression in gastric cancer (GC) compared with that in normal tissues and gastric cell lines.Methods: USP19 protein expression was analyzed in 212 paired GC samples using immunohistochemical staining. Quantitative real-time PCR (qRT-PCR) and Western blotting were used to detect the level of USP19 in gastric cell lines. The biological functions of USP19 were investigated by MTT assay, colony-forming assay, wound healing assay and gelatin zymography, and apoptotic cells were detected by immunohistochemistry assays in SGC7901 xenograft models.Results: USP19 expression was significantly increased in GC cells and tissues, and the high level of USP19 expression was positively correlated with the Lauren’s classification and poor prognosis. Moreover, USP19 was identified as a novel independent prognostic biomarker in GC patients. Enhanced USP19 expression promoted GC cell proliferation and metastasis through reduced cleaved caspase-3 and increased MMP2/MMP9 expression and promoted enzyme activity in the study, and verified the results through The Cancer Genome Atlas (TCGA) and bioinformatic websites from the Kaplan–Meier plotter (http://kmplot.com) and GEPIA (http://gepia2.cancer-pku.cn.).Conclusion: Our study suggests that USP19 promoted tumor progression by inducing MMP2/MMP9 expression and related enzyme activity. Hence, USP19 may be a valuable prognostic predictor for GC, and the USP19-MMP2/MMP9 axis could serve as a therapeutic target.Keywords: USP19, MMP2/MMP9, gastric cancer, prognosis, invasion, metastasis, TCGA

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