title: MicroRNA-224 sustains Wnt/β-catenin signaling and promotes aggressive phenotype of colorectal cancer.
abstract: 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.
  
  
  CONCLUSIONS
  Our research showed mechanistic links between miR-224 and Wnt/β-catenin in the pathogenesis of CRC through modulation of GSK3β and SFRP2.
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China. 343730051@qq.com.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China. 343730051@qq.com.|State Key Laboratory of Oncology in Southern China, Department of Experimental, Guangzhou, Guangdong, China. 343730051@qq.com.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China. 1242196935@qq.com.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China. 1242196935@qq.com.|State Key Laboratory of Oncology in Southern China, Department of Experimental, Guangzhou, Guangdong, China. 1242196935@qq.com.
authors.forename: Qiuhua
authors.initials: Q
authors.lastname: Lai
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China. 892017647@qq.com.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China. 892017647@qq.com.|State Key Laboratory of Oncology in Southern China, Department of Experimental, Guangzhou, Guangdong, China. 892017647@qq.com.
authors.forename: Shuyang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China. 834957861@qq.com.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China. 834957861@qq.com.|State Key Laboratory of Oncology in Southern China, Department of Experimental, Guangzhou, Guangdong, China. 834957861@qq.com.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China. 865872768@qq.com.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China. 865872768@qq.com.|State Key Laboratory of Oncology in Southern China, Department of Experimental, Guangzhou, Guangdong, China. 865872768@qq.com.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China. 842190983@qq.com.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China. 842190983@qq.com.|State Key Laboratory of Oncology in Southern China, Department of Experimental, Guangzhou, Guangdong, China. 842190983@qq.com.
authors.forename: Danling
authors.initials: D
authors.lastname: Deng
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China. 947052567@qq.com.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China. 947052567@qq.com.|State Key Laboratory of Oncology in Southern China, Department of Experimental, Guangzhou, Guangdong, China. 947052567@qq.com.
authors.forename: Liuqing
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China. 25048195@qq.com.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China. 25048195@qq.com.|State Key Laboratory of Oncology in Southern China, Department of Experimental, Guangzhou, Guangdong, China. 25048195@qq.com.
authors.forename: Hongli
authors.initials: H
authors.lastname: Jiao
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China. 149941225@qq.com.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China. 149941225@qq.com.|State Key Laboratory of Oncology in Southern China, Department of Experimental, Guangzhou, Guangdong, China. 149941225@qq.com.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China. lli@fimmu.com.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China. lli@fimmu.com.|State Key Laboratory of Oncology in Southern China, Department of Experimental, Guangzhou, Guangdong, China. lli@fimmu.com.
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China. dyq@fimmu.com.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China. dyq@fimmu.com.|State Key Laboratory of Oncology in Southern China, Department of Experimental, Guangzhou, Guangdong, China. dyq@fimmu.com.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China. liaowt2002@gmail.com.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China. liaowt2002@gmail.com.|State Key Laboratory of Oncology in Southern China, Department of Experimental, Guangzhou, Guangdong, China. liaowt2002@gmail.com.
authors.forename: Wenting
authors.initials: W
authors.lastname: Liao
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics; D000071679:Glycogen Synthase Kinase 3 beta; D045325:HCT116 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000473:pathology; D009368:Neoplasm Transplantation; D060449:Wnt Signaling Pathway; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D020413:3' Untranslated Regions; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D008565:Membrane Proteins; D035683:MicroRNAs; C546140:MIRN224 microRNA, human; C109618:SFRP2 protein, human; D000094742:Secreted Frizzled-Related Proteins; C000605506:GSK3B protein, human; C000605507:Gsk3b protein, mouse
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