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MicroRNA-224 sustains Wnt/β-catenin signaling and promotes aggressive phenotype of colorectal cancer
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نویسنده
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li t. ,lai q. ,wang s. ,cai j. ,xiao z. ,deng d. ,he l. ,jiao h. ,ye y. ,liang l. ,ding y. ,liao w.
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منبع
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journal of experimental and clinical cancer research - 2016 - دوره : 35 - شماره : 1
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چکیده
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Background: growing evidence suggests that wnt/β-catenin pathway plays an important role in crc development,progression and metastasis. aberrant mir-224 expression has been reported in crc. however,the mechanism of mir-224 promotes both proliferation and metastatic ability largely remains unclear. methods: real-time pcr was used to quantify mir-224 expression. luciferase reporter assays were conducted to confirm the activity of wnt/β-catenin pathway and target gene associations,and immunofluorescence staining assay was performed to observe the nuclear translocation of β-catenin. bioinformatics analysis combined with in vivo and vitro functional assays showed the potential target genes,gsk3β and sfrp2,of mir-224. specimens from forty patients with crc were analyzed for the expression of mir-224 and the relationship with gsk3β/sfrp2 by real-time pcr and western blot. results: bioinformatics and cell luciferase function studies verified the direct regulation of mir-224 on the 3'-utr of the gsk3β and sfrp2 genes,which leads to the activation of wnt/β-catenin signaling and the nuclear translocation of β-catenin. in addition,knockdown of mir-224 significantly recovered the expression of gsk3β and sfrp2 and attenuated wnt/β-catenin-mediated cell metastasis and proliferation. the ectopic upregulation of mir-224 dramatically inhibited the expression of gsk3β/sfrp2 and enhanced crc proliferation and invasion. conclusion: our research showed mechanistic links between mir-224 and wnt/β-catenin in the pathogenesis of crc through modulation of gsk3β and sfrp2. © 2016 li et al.
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کلیدواژه
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Colorectal cancer; GSK3β; Invasion; miR-224; Proliferation; SFRP2; Wnt/β-catenin
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آدرس
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department of pathology,nanfang hospital,southern medical university,guangzhou,guangdong,510515,china,department of pathology,school of basic medical sciences,southern medical university,guangzhou,guangdong,china,state key laboratory of oncology in southern china,department of experimental china,guangzhou,guangdong, China, department of pathology,nanfang hospital,southern medical university,guangzhou,guangdong,510515,china,department of pathology,school of basic medical sciences,southern medical university,guangzhou,guangdong,china,state key laboratory of oncology in southern china,department of experimental china,guangzhou,guangdong, China, department of pathology,nanfang hospital,southern medical university,guangzhou,guangdong,510515,china,department of pathology,school of basic medical sciences,southern medical university,guangzhou,guangdong,china,state key laboratory of oncology in southern china,department of experimental china,guangzhou,guangdong, China, department of pathology,nanfang hospital,southern medical university,guangzhou,guangdong,510515,china,department of pathology,school of basic medical sciences,southern medical university,guangzhou,guangdong,china,state key laboratory of oncology in southern china,department of experimental china,guangzhou,guangdong, China, department of pathology,nanfang hospital,southern medical university,guangzhou,guangdong,510515,china,department of pathology,school of basic medical sciences,southern medical university,guangzhou,guangdong,china,state key laboratory of oncology in southern china,department of experimental china,guangzhou,guangdong, China, department of pathology,nanfang hospital,southern medical university,guangzhou,guangdong,510515,china,department of pathology,school of basic medical sciences,southern medical university,guangzhou,guangdong,china,state key laboratory of oncology in southern china,department of experimental china,guangzhou,guangdong, China, department of pathology,nanfang hospital,southern medical university,guangzhou,guangdong,510515,china,department of pathology,school of basic medical sciences,southern medical university,guangzhou,guangdong,china,state key laboratory of oncology in southern china,department of experimental china,guangzhou,guangdong, China, department of pathology,nanfang hospital,southern medical university,guangzhou,guangdong,510515,china,department of pathology,school of basic medical sciences,southern medical university,guangzhou,guangdong,china,state key laboratory of oncology in southern china,department of experimental china,guangzhou,guangdong, China, department of pathology,nanfang hospital,southern medical university,guangzhou,guangdong,510515,china,department of pathology,school of basic medical sciences,southern medical university,guangzhou,guangdong,china,state key laboratory of oncology in southern china,department of experimental china,guangzhou,guangdong, China, department of pathology,nanfang hospital,southern medical university,guangzhou,guangdong,510515,china,department of pathology,school of basic medical sciences,southern medical university,guangzhou,guangdong,china,state key laboratory of oncology in southern china,department of experimental china,guangzhou,guangdong, China, department of pathology,nanfang hospital,southern medical university,guangzhou,guangdong,510515,china,department of pathology,school of basic medical sciences,southern medical university,guangzhou,guangdong,china,state key laboratory of oncology in southern china,department of experimental china,guangzhou,guangdong, China, department of pathology,nanfang hospital,southern medical university,guangzhou,guangdong,510515,china,department of pathology,school of basic medical sciences,southern medical university,guangzhou,guangdong,china,state key laboratory of oncology in southern china,department of experimental china,guangzhou,guangdong, China
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