title: Deregulated expression of sprouty2 and microRNA-21 in human colon cancer: Correlation with the clinical stage of the disease.
abstract: Sprouty protein is a novel feedback regulator involved in downstream inactivation of several growth factor receptor pathways. Sprouty2 (Spry2) protein was shown to be downregulated in human cancers. High levels of microRNA-21 (miRNA-21) expression have been associated with poor survival and poor response to adjuvant chemotherapy in cancer patients. But the effect of Spry2 in human colon cancer remained unknown. Paired tumor and normal mucosa samples from patients were examined for their expression of Spry2 mRNA and miRNA-21 by real-time quantitative RT-PCR analysis. Our results show that Spry2 was downregulated in human colon cancer, and its expression levels were lower in advanced-stage tumors than in early-stage tumors. There was a negative correlation between the expression levels of Spry2 and miRNA-21. Furthermore, overexpression of Spry2 suppressed the growth and migration of colon cancer cells with a concomitant increase in PTEN expression and reduction of Akt and MAPK phosphorylation. Spry2 inhibited the growth and tumorigenesis of colon cancer cells in vivo. Conclusively, we show for the first time that Spry2 expression is downregulated and miRNA-21 is upregulated in the clinical samples of colon cancer, which correlates with clinical stage of disease. Thus, Spry2 functions as a tumor suppressor in colon cancer.
authors.affiliation: National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yin-Hsun
authors.initials: YH
authors.lastname: Feng
authors.forename: Chao-Liang
authors.initials: CL
authors.lastname: Wu
authors.forename: Chao-Jung
authors.initials: CJ
authors.lastname: Tsao
authors.forename: Jan-Gowth
authors.initials: JG
authors.lastname: Chang
authors.forename: Pei-Jung
authors.initials: PJ
authors.lastname: Lu
authors.forename: Kun-Tu
authors.initials: KT
authors.lastname: Yeh
authors.forename: Yih-Huei
authors.initials: YH
authors.lastname: Uen
authors.forename: Jeng-Chang
authors.initials: JC
authors.lastname: Lee
authors.forename: Ai-Li
authors.initials: AL
authors.lastname: Shiau
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D016147:Genes, Tumor Suppressor; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014162:Transfection; D014183:Transplantation, Heterologous
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C524940:MIRN21 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C485561:SPRY2 protein, human; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human