Down-regulation Of Ubiquitin-specific Protease 22(USP22) Inhibits Invasion,Metastasis And Epithelial-mesenchymal Transition Of Gastric Cancer

Background and ObjectiveUbiquitin-specific protease 22(USP 22)is a member of the ubiquitin-specific protease(USPs)family and belongs to the family of deubiquitinases.The ubiquitinspecific protease is the largest and most specific subfamily of the deubiquitinase family,with species and tissue specificity,and its core catalytic domain consists of approximately 350 amino acids.These enzymes contain two short and conserved fragments of the lysine cassette and the histidine cassette,which remove ubiquitin molecules from the relatively high molecular weight protein substrate and participate in recycling.Therefore,ubiquitin-specific proteases can regulate the transcription of downstream genes by deubiquitinating histones,thereby regulating the occurrence and development of tumors.USP22 was identified as a conserved component of the human chromatin recombination complex,the SAGA(Spt-Ada-Gcn5 acetyltransferase)transcriptional regulatory complex,and USP22 regulates gene transcription by its single deubiquitination of histones H2 A and H2 B.In addition,the study found that USP22 promotes the stability of a variety of cancer-associated target proteins by deubiquitination and thus affects oncogene accumulation,or uses deubiquitination as a means of regulating protein function and promoting cell proliferation.Up-regulation of USP22 expression is associated with development and poor prognosis in a variety of cancers.Based on the above background,this paper aims to explore the biological effects of USP22 on the development and lymph node metastasis of gastric cancer and its mechanism through related experimental studies.Methods1.Collect and analyze the clinical data of 62 patients: age,gender,tumor pathological TNM staging,degree of differentiation,lymph node metastasis,etc.2.The expression of USP22 protein in gastric cancer tissues and paraffin sections of normal gastric mucosa tissues was detected by immunohistochemical staining.The expression of USP22 protein in gastric cancer cells MGC-803 and SGC-7901 was detected by Western blot.3.The siRNA silencing of USP22 was designed.The cycle changes and apoptosis of gastric cancer cells MGC-803 were detected by flow cytometry.The levels of EMTrelated proteins in MGC-803 were detected by Western blot.4.Cell proliferation was detected by MTT assay,and cell invasion ability was detected by cell invasion assay.Results1.USP22 is highly expressed in gastric cancer tissues and gastric cancer cell lines,and has a close relationship with pathological TNM staging and tumor differentiation.2.Down-regulation of USP22 can inhibit gastric cancer cell proliferation and invasive ability in vitro,and the inhibitory effect increases with time.3.Down-regulation of USP22 can inhibit the occurrence of EMT process in gastric cancer cells.Significantly increased expression of E-cadherin(epithelial marker)while reducing expression of N-cadherin and vimentin(mesenchymal markers).4.Down-regulation of USP22 can promote apoptosis and arrest the cell cycle in G0/G1 phase.ConclusionsDownregulation of ubiquitin-specific protease 22 can inhibit gastric cancer proliferation,migration and metastasis,and can inhibit EMT process in gastric cancer.