title: WWP1 as a potential tumor oncogene regulates PTEN-Akt signaling pathway in human gastric carcinoma.
abstract: Whelming evidence has demonstrated that WW domain containing E3 ubiquitin protein ligase 1 (WWP1) participates in a wide variety of biological processes and is tightly related to the initiation and progression of many tumors. Currently, although mounting evidence supports a role of WWP1 in tumor promotion and tumorigenesis, the potential roles of WWP1 and its biological functions in gastric carcinoma are not fully understood. Here, we found that WWP1 messenger RNA (mRNA) and protein were highly expressed in gastric carcinoma tissues and cells. High WWP1 mRNA and protein levels were tightly related to differentiation status, TNM stage, invasive depth, lymph node metastasis, and poor prognosis in gastric carcinoma. Furthermore, WWP1 siRNA significantly decreased WWP1 protein level in MKN-45 and AGS cells; meanwhile, WWP1 depletion markedly inhibited tumor proliferation in vitro and in vivo, arrested cell cycle at G0/G1 phase, and induced cell apoptosis in MKN-45 and AGS cells. Most notably, WWP1 downregulation both inactivated PTEN-Akt signaling pathway in MKN-45 and AGS cells. Taken altogether, our findings suggest that WWP1 acts as an oncogenic factor and should be considered as a novel interfering molecular target for gastric carcinoma.
authors.affiliation: Department of Histology and Embryology, Basic Medical College of Zhengzhou University, 100 Kexue Road, Zhengzhou, Henan, 450001, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Zongyin
authors.initials: Z
authors.lastname: Wu
authors.forename: Zhao
authors.initials: Z
authors.lastname: Ma
authors.forename: Hongtao
authors.initials: H
authors.lastname: Liu
authors.forename: Yahong
authors.initials: Y
authors.lastname: Wu
authors.forename: Qinxian
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D051058:Oncogene Protein v-akt / Q000096:biosynthesis* / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C471642:WWP1 protein, human; D044767:Ubiquitin-Protein Ligases; D051058:Oncogene Protein v-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human