title: Let-7b inhibits cell proliferation, migration, and invasion through targeting Cthrc1 in gastric cancer.
abstract: Dysregulation of specific microRNAs (miRNAs) is found to play a vital role in carcinogenesis and progression of gastric cancer (GC). In the present study, we investigated the expression profiles of miRNAs in gastric cancer. Let-7b was found downregulated remarkably in gastric cancer tissues and was correlated with Helicobacter pylori infection, tumor stage, and lymphatic metastasis. Ectopic expression of let-7b suppressed the growth, migration, invasion, and tumorigenicity of GC cells, whereas let-7b knockdown promoted these phenotypes. Bioinformatic analysis predicted collagen triple helix repeat containing 1 (Cthrc1) as a direct target of let-7b. Luciferase assay showed that let-7b repressed the activity of Cthrc1 through binding its 3'UTR. Western blotting also confirmed that the protein levels of Cthrc1 were decreased by let-7b. Cthrc1 was significantly upregulated and reversely correlated with let-7b levels in GC. Co-expression of let-7b and Cthrc1 without its 3'UTR could rescue cell growth, migration, and invasion inhibited by let-7b. These results suggest that let-7b may directly target Cthrc1 and function as a tumor suppressor gene in GC.
authors.affiliation: Department of General Surgery, the Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Junbo
authors.initials: J
authors.lastname: Yu
authors.forename: Jin
authors.initials: J
authors.lastname: Feng
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Zhi
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.forename: Zenliang
authors.initials: Z
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Zekuan
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D034622:RNA Interference; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D047368:Tumor Burden
chemical_list: C502426:CTHRC1 protein, human; D016326:Extracellular Matrix Proteins; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human