title: TRIM25 blockade by RNA interference inhibited migration and invasion of gastric cancer cells through TGF-β signaling.
abstract: Tripartite Motif Containing 25 (TRIM25), a member of TRIM proteins, has been found abnormally expressed in cancers of female reproductive system. Here, TRIM25 was conspicuously expressed in human gastric cancer (GC) tissues in which its higher expression generally correlated with the poor prognosis of patients. Small interfering RNA (siRNA)-mediated knockdown of TRIM25 expression in MGC-803 and AGS cells had no effects on cell proliferation, whereas reduced cell migration and invasion. Gene set enrichment analysis on The Cancer Genome Atlas stomach adenocarcinoma (STAD) dataset revealed that several signaling pathways, including the migration, E-cadherin and transforming growth factor-β (TGF-β) pathways, were enriched in TRIM25 higher expression patients. Moreover, ectopic expression of TRIM25 in a GC cell line with lower expression of TRIM25 significantly promoted the migration and invasion. Further experiments with TGF-β inhibitor suggested that TRIM25 may exert its function through TGF-β pathway. In summary, our results indicate that TRIM25 acts as an oncogene in GC and thus presents a novel target for the detection and treatment of GC.
authors.affiliation: Department of General Surgery, Shanghai Pudong District People's Hospital, Shanghai 201299, China.
authors.forename: Zhenya
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Punan Hospital, Pudong New District, Shanghai 200125, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Shanghai Pudong District People's Hospital, Shanghai 201299, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Shanghai Pudong District People's Hospital, Shanghai 201299, China.
authors.forename: Shiyong
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of General Surgery, Shanghai Pudong District People's Hospital, Shanghai 201299, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Shanghai Pudong District People's Hospital, Shanghai 201299, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Hou
authors.affiliation: Department of General Surgery, Shanghai Pudong District People's Hospital, Shanghai 201299, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
mesh_terms: D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D009362:Neoplasm Metastasis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D000070584:Tripartite Motif Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D015820:Cadherins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D000070584:Tripartite Motif Proteins; C084523:TRIM25 protein, human; D044767:Ubiquitin-Protein Ligases