title: Long non-coding RNA linc00261 suppresses gastric cancer progression via promoting Slug degradation.
abstract: Gastric cancer (GC) remains a threat to public health with high incidence and mortality worldwide. Increasing evidence demonstrates that long non-coding RNAs (lncRNAs) play critical regulatory roles in cancer biology, including GC. Previous profiling study showed that lncRNA linc00261 was aberrantly expressed in GC. However, the role of linc00261 in GC progression and the precise molecular mechanism remain unknown. In this study, we report that linc00261 was significantly down-regulated in GC tissues and the expression level of linc00261 negatively correlated with advanced tumour status and clinical stage as well as poor prognostic outcome. In vitro functional assays indicate that ectopic expression of linc00261 suppressed cell invasion by inhibiting the epithelial-mesenchymal transition (EMT). By RNA pull-down and mass spectrum experiments, we identified Slug as an RNA-binding protein that binds to linc00261. We confirmed that linc00261 down-regulated Slug by decreasing the stability of Slug proteins and that the tumour-suppressive function of linc00261 can be neutralized by Slug. linc00261 may promote the degradation of Slug via enhancing the interaction between GSK3β and Slug. Moreover, linc00216 overexpression repressed lung metastasis in vivo. Together, our findings suggest that linc00261 acts a tumour suppressor in GC by decreasing the stability of Slug proteins and suppressing EMT. By clarifying the mechanisms underlying GC progression, these findings may facilitate the development of novel therapeutic strategies for GC.
authors.affiliation: Department of Gastroenterology, The Third Clinical College of Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou, China.
authors.forename: Yingcong
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Urology Surgery, The Third Clinical College of Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou, China.
authors.forename: Linjin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of General Surgery, The Second Affilated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of General Surgery, The Third Clinical College of Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou, China.
authors.forename: Senrui
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of General Surgery, The Third Clinical College of Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou, China.
authors.forename: Ende
authors.initials: E
authors.lastname: Chen
authors.affiliation: Department of General Surgery, The Third Clinical College of Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou, China.
authors.forename: Yiren
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D011379:Prognosis; D011485:Protein Binding; D059748:Proteolysis; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D000071250:Snail Family Transcription Factors / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D062085:RNA, Long Noncoding; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C000623252:long non-coding RNA 00261, human; D000071679:Glycogen Synthase Kinase 3 beta
keywords: Slug; epithelial-mesenchymal transition; gastric cancer; invasion; long non-coding RNA