title: IGF2-derived miR-483 mediated oncofunction by suppressing DLC-1 and associated with colorectal cancer.
abstract: Emerging evidence indicates that IGF2 plays an important role in various human malignancies, including colorectal cancer (CRC). Hsa-miR-483 is located within intron 7 of the IGF2 locus. However, the mechanism by which increased IGF2 induces carcinogenesis remains largely elusive. DLC-1 has been identified as a candidate tumor suppressor. In this study, we aimed at investigating whether miR-483 transcription is IGF2-dependent, identifying the functional target of miR-483, and evaluating whether tissue and serum miR-483-3p or miR-483-5p levels are associated with CRC. Our results showed that sequences upstream miR-483 had undetectable promoter activity and levels of IGF2, miR-483-3p, and miR-483-5p were synchronously increased in CRC tissues. Positive correlations between IGF2 and miR-483-3p (r=0.4984, ***p<0.0001), and between IGF2 and miR-483-5p (r=0.6659, ***p<0.0001) expression were found. In addition, patients with CRC had a significantly higher serum miR-483-5p level (*p<0.05) compared to normal controls. DLC-1 expression was decreased in colorectal cancer tissues and diminished through transient transfection with miR-483-3p. Our results suggest that IGF2 may exert its oncofunction, at least partly, through its parasitic miR-483 which suppressed DLC-1 in CRC cells. Thus, miR-483 might serve as a new target for therapy and a potential biomarker for the detection of colorectal cancer.
authors.affiliation: Institute of Epigenetics and Epigenomics, Institute of Comparative Medicine and College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China.|Laboratory of Epigenetics & Epigenomics, Medical School, Nanjing University, Nanjing, China.|Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.
authors.forename: Hengmi
authors.initials: H
authors.lastname: Cui
authors.affiliation: Laboratory of Epigenetics & Epigenomics, Medical School, Nanjing University, Nanjing, China.|Department of Gastroenterology, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China.|Quzhou People's Hospital, Quzhou, Zhengjiang, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Laboratory of Epigenetics & Epigenomics, Medical School, Nanjing University, Nanjing, China.|Department of Gastroenterology, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China.|Xuzhou Cancer Hospital, Xuzhou, Jiangsu, China.
authors.forename: Jingrui
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Institute of Epigenetics and Epigenomics, Institute of Comparative Medicine and College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China.|Laboratory of Epigenetics & Epigenomics, Medical School, Nanjing University, Nanjing, China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Epigenetics and Epigenomics, Institute of Comparative Medicine and College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China.|Laboratory of Epigenetics & Epigenomics, Medical School, Nanjing University, Nanjing, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Laboratory of Epigenetics & Epigenomics, Medical School, Nanjing University, Nanjing, China.|Department of Gastroenterology, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China.
authors.forename: Shaogen
authors.initials: S
authors.lastname: Wu
authors.affiliation: Laboratory of Epigenetics & Epigenomics, Medical School, Nanjing University, Nanjing, China.
authors.forename: Wangsen
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Pathology and Laboratory Medicine, New York Presbyterian-Weill Cornell Medicine, New York, USA.
authors.forename: Isabelle H
authors.initials: IH
authors.lastname: Cui
authors.affiliation: Laboratory of Epigenetics & Epigenomics, Medical School, Nanjing University, Nanjing, China.|Department of Gastroenterology, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China.
authors.forename: Chenggong
authors.initials: C
authors.lastname: Yu
mesh_terms: D000070416:Antagomirs / Q000378:metabolism; D014408:Biomarkers, Tumor; D001706:Biopsy; D063646:Carcinogenesis / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D003106:Colon / Q000473:pathology; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation; D005240:Feasibility Studies; D020690:GTPase-Activating Proteins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000032:analysis* / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D000070416:Antagomirs; D014408:Biomarkers, Tumor; C112352:DLC1 protein, human; D020690:GTPase-Activating Proteins; C035170:IGF2 protein, human; C548912:MIRN483 microRNA, human; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins; D007335:Insulin-Like Growth Factor II
keywords: DLC-1; IGF2; colorectal cancer; miR-483