title: Regulation of colorectal carcinoma stemness, growth, and metastasis by an miR-200c-Sox2-negative feedback loop mechanism.
abstract: OBJECTIVE
  To elucidate a novel mechanism of miR-200c in the regulation of stemness, growth, and metastasis in colorectal carcinoma (CRC).
  
  
  METHODS
  Quantitative reverse transcription PCR was used to quantify miR-200c expression in CRC cell lines and tissues. A luciferase assay was adopted for the target evaluation. The functional effects of miR-200c in CRC cells were assessed by its forced or inhibited expression using lentiviruses.
  
  
  RESULTS
  MiR-200c was statistically lower in CRC clinical specimens and highly metastatic CRC cell lines compared with their counterparts. Sox2 was validated as a target for miR-200c. The knockdown of miR-200c significantly enhanced proliferation, migration, and invasion in CRC cell lines, whereas the upregulation of miR-200c exhibited an inverse effect. Moreover, rescue of Sox2 expression could abolish the effect of the upregulation of miR-200c. In addition, the reduction of miR-200c increased the expression of CRC stem cell markers and the sphere-forming capacity of CRC cell lines. Further study has shown that miR-200c and Sox2 reciprocally control their expression through a feedback loop. MiR-200c suppresses the expression of Sox2 to block the activity of the phosphoinositide 3-kinase (PI3K)-AKT pathway.
  
  
  CONCLUSIONS
  Our findings indicate that miR-200c regulates Sox2 expression through a feedback loop and is associated with CRC stemness, growth, and metastasis.
authors.affiliation: Authors' Affiliations: Department of Pathology, School of Basic Medical Sciences, Department of Pathology, Nanfang Hospital, Southern Medical University, Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou; and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Lu
authors.affiliation: Authors' Affiliations: Department of Pathology, School of Basic Medical Sciences, Department of Pathology, Nanfang Hospital, Southern Medical University, Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou; and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Authors' Affiliations: Department of Pathology, School of Basic Medical Sciences, Department of Pathology, Nanfang Hospital, Southern Medical University, Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou; and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Xiao-Lei
authors.initials: XL
authors.lastname: Xue
authors.affiliation: Authors' Affiliations: Department of Pathology, School of Basic Medical Sciences, Department of Pathology, Nanfang Hospital, Southern Medical University, Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou; and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Authors' Affiliations: Department of Pathology, School of Basic Medical Sciences, Department of Pathology, Nanfang Hospital, Southern Medical University, Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou; and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Authors' Affiliations: Department of Pathology, School of Basic Medical Sciences, Department of Pathology, Nanfang Hospital, Southern Medical University, Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou; and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaAuthors' Affiliations: Department of Pathology, School of Basic Medical Sciences, Department of Pathology, Nanfang Hospital, Southern Medical University, Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou; and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Authors' Affiliations: Department of Pathology, School of Basic Medical Sciences, Department of Pathology, Nanfang Hospital, Southern Medical University, Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou; and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Li
authors.affiliation: Authors' Affiliations: Department of Pathology, School of Basic Medical Sciences, Department of Pathology, Nanfang Hospital, Southern Medical University, Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou; and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Authors' Affiliations: Department of Pathology, School of Basic Medical Sciences, Department of Pathology, Nanfang Hospital, Southern Medical University, Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou; and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Hong
authors.affiliation: Authors' Affiliations: Department of Pathology, School of Basic Medical Sciences, Department of Pathology, Nanfang Hospital, Southern Medical University, Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou; and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China nfydlxn@126.com.
authors.forename: Xue-Nong
authors.initials: XN
authors.lastname: Li
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D025461:Feedback, Physiological; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000235:genetics
chemical_list: C533896:MIRN200 microRNA, human; D035683:MicroRNAs; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt