title: Catenin-δ1, negatively regulated by miR-145, promotes tumour aggressiveness in gastric cancer.
abstract: Increasing evidence supports the association of catenin-δ1 (CTNND1, p120ctn) with tumour development and progression. However, the mechanism and clinical significance of CTNND1 deregulation in gastric cancer remain unknown. The expression level and cellular localization of CTNND1 were determined by immunohistochemistry in 126 human gastric cancer and 50 non-tumourous tissues. The cellular localization of CTNND1 and epithelial cadherin (E-cadherin) were detected by immunofluorescence. Cell proliferation, apoptosis, migration and invasion assays were performed to assess the effect of CTNND1 cDNA or CTNND1 siRNA transfection on gastric cancer cells. Luciferase assay, western blot analysis and in vivo assays were used to determine whether CTNND1 could be regulated by miR-145. The results demonstrate that the cytoplasmic localization of CTNND1 protein, rather than expression level, was indicative of higher clinical stage, positive lymph node metastasis and poorer prognosis in gastric cancers. CTNND1 could promote gastric cancer cell migration and invasion with little effect on cellular proliferation and apoptosis. CTNND1 was proved to be a direct target gene for miR-145. Besides suppressing cytoplasmic CTNND1 expression, miR-145 could recover the membranous localization of CTNND1 and E-cadherin. We conclude that cytoplasmic CTNND1 can serve as an independent prognostic factor for patients with gastric cancers. MiR-145 inhibits invasion of gastric cancer cells not only by down-regulating cytoplasmic CTNND1 expression but also by inducing the translocation of CTNND1 and E-cadherin from the cytoplasm to the cell membrane through down-regulating N-cadherin.
authors.affiliation: Department of Pathology, School of Medicine, Shandong University, Jinan, People's Republic of China.
authors.forename: Ai-Yan
authors.initials: AY
authors.lastname: Xing
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Wang
authors.forename: Zhong-Xue
authors.initials: ZX
authors.lastname: Su
authors.forename: Duan-Bo
authors.initials: DB
authors.lastname: Shi
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051177:Catenins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000095002:Delta Catenin
chemical_list: D051177:Catenins; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D000095002:Delta Catenin; C000722347:CTNND1 protein, human
keywords: CTNND1; E-cadherin; gastric cancer; invasion; miR-145