title: MicroRNA let-7b suppresses human gastric cancer malignancy by targeting ING1.
abstract: MicroRNAs (miRNAs) are important regulators that play key roles in tumorigenesis and tumor progression. In this study, we investigate whether let-7b acts as a tumor suppressor to inhibit invasion and metastasis in gastric cancers. We analyzed the expression of let-7b in 60 pair-matched gastric neoplastic and adjacent non-neoplastic tissues by quantitative real-time polymerase chain reaction. Functional analysis of let-7b expression was assessed in vitro in gastric cancer cell lines with let-7b precursor and inhibitor. The roles of let-7b in tumorigenesis and tumor metastasis were analyzed using a stable let-7b expression plasmid in nude mice. A luciferase reporter assay was used to assess the effect of let-7b on inhibitor of growth family, member 1 (ING1) expression. Real-time PCR showed decreased levels of let-7b expression in metastatic gastric cancer tissues and cell lines that are potentially highly metastatic. Cell invasion and migration were significantly impaired in GC9811-P and SGC7901-M cell lines after transfection with let-7b mimics. Nude mice with xenograft models of gastric cancer confirmed that let-7b could inhibit gastric cancer metastasis in vivo after transfection by the lentivirus pGCsil-GFP- let-7b. Luciferase reporter assays demonstrated that let-7b directly binds to the 3'-UTR of ING1, and real-time PCR and western blotting further indicated that let-7b downregulated the expression of ING1 at the mRNA and protein levels. Our study demonstrates that overexpression of let-7b in gastric cancer can inhibit invasion and migration of gastric cancer cells through directly targeting the tumor metastasis-associated gene ING1. These findings help clarify the molecular mechanisms involved in gastric cancer metastasis and indicate that let-7b modulation may be a bona fide treatment of gastric cancer.
authors.affiliation: Internal Medicine-Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
authors.forename: X
authors.initials: X
authors.lastname: Han
authors.affiliation: Surgical oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
authors.forename: N
authors.initials: N
authors.lastname: Yao
authors.affiliation: Department of Pharmacology, Bengbu Medical College, Bengbu, Anhui, China.
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.affiliation: Internal Medicine-Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D000818:Animals; D001665:Binding Sites; D063646:Carcinogenesis / Q000235:genetics; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; C487931:mirnlet7 microRNA, human