title: KITLG is a novel target of miR-34c that is associated with the inhibition of growth and invasion in colorectal cancer cells.
abstract: MiR-34c is considered a potent tumour suppressor because of its negative regulation of multiple target mRNAs that are critically associated with tumorigenesis and metastasis. In the present study, we demonstrated a novel target of miR-34c, KITLG, which has been implicated in colorectal cancer (CRC). First, we found a significant negative relationship between miR-34c and KITLG mRNA expression levels in CRC cell lines, including HT-29, HCT-116, SW480 and SW620 CRC cell lines. In silico analysis predicted putative binding sites for miR-34c in the 3' untranslated region (3'UTR) of KITLG mRNA. A dual-luciferase reporter assay further confirmed that KITLG is a direct target of miR-34c. Then, the cell lines were infected with lentiviruses expressing miR-34c or a miR-34c specific inhibitor. Restoration of miR-34c dramatically reduced the expression of KITLG mRNA and protein, while silencing of endogenous miR-34c increased the expression of KITLG protein. The miR-34c-mediated down-regulation of KITLG was associated with the suppression on proliferation, cellular transformation, migration and invasion of CRC cells, as well as the promotion on apoptosis. Knockdown of KITLG by its specific siRNA confirmed a critical role of KITLG down-regulation for the tumour-suppressive effects of miR-34c in CRC cells. In conclusion, our results demonstrated that miR-34c might interfere with KITLG-related CRC and could be a novel molecular target for CRC patients.
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Yang
authors.forename: Wen-shuai
authors.initials: WS
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Dong
authors.forename: Hai-mei
authors.initials: HM
authors.lastname: Sun
authors.forename: Bo
authors.initials: B
authors.lastname: Wu
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
authors.forename: Wan-jing
authors.initials: WJ
authors.lastname: Zou
authors.forename: De-shan
authors.initials: DS
authors.lastname: Zhou
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control*; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019089:Stem Cell Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019089:Stem Cell Factor
keywords: KITLG; colorectal cancer cell; miR-34c; tumour suppressor