title: MicroRNA-29a promotes colorectal cancer metastasis by regulating matrix metalloproteinase 2 and E-cadherin via KLF4.
abstract: BACKGROUND
  Growing evidence suggests that miR-29a has an important role in regulating tumourigenesis and development of various types of cancer. However, the role and the underlying mechanism of miR-29a in colorectal cancer (CRC) remain largely unknown.
  
  
  METHODS
  MiR-29a targeted gene was identified by the luciferase assay and western blot. MiR-29a function was analysed by invasion assays and the orthotopic transplantation mouse model. The miR-29a pathway was assayed by real-time PCR, western blot and chip analysis.
  
  
  RESULTS
  KLF4 was identified as a direct target gene of miR-29a. MiR-29a promoted CRC cell invasion, which was blocked by re-expression of KLF4. In addition, MMP2 was identified as a novel direct target of KLF4. Both miR-29a overexpression and KLF4 knockdown promoted MMP2 expression but inhibited E-cadherin expression. Furthermore, clinical data indicated that both miR-29a high expression and KLF4 mRNA low expression were associated with metastasis and poor prognosis in CRC patients, and KLF4 protein expression was inversely correlated with MMP2 but positively correlated with E-cad protein expression.
  
  
  CONCLUSIONS
  Increased expression of miR-29a promoted CRC metastasis by regulating MMP2/E-cad through direct targeting KLF4, which highlights the potential of the miR-29a inhibitor as a novel agent against CRC metastasis.
authors.affiliation: 1] Department of Colorectal Surgery, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China [2] Department of General Surgery, Second Affiliated Hospital to Yangzhou University School of Medicine, No. 45 Taizhou Road, Yangzhou 225001, China.
authors.forename: W
authors.initials: W
authors.lastname: Tang
authors.affiliation: 1] Department of Colorectal Surgery, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China [2] Department of General Surgery, Second Affiliated Hospital to Yangzhou University School of Medicine, No. 45 Taizhou Road, Yangzhou 225001, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology, Changhai Hospital affiliated to Second Military Medical University, No. 168 Changhai Road, Shanghai 200433, China.
authors.forename: J
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Colorectal Surgery, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: J
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Colorectal Surgery, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Colorectal Surgery, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital affiliated to Tongji University School of Life Science and Technology, No. 1239 Siping Road, Shanghai 200092, China.
authors.forename: C
authors.initials: C
authors.lastname: Song
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital affiliated to Tongji University School of Life Science and Technology, No. 1239 Siping Road, Shanghai 200092, China.
authors.forename: S
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital affiliated to Tongji University School of Life Science and Technology, No. 1239 Siping Road, Shanghai 200092, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Leng
authors.affiliation: Department of Colorectal Surgery, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Colorectal Surgery, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Colorectal Surgery, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: P
authors.initials: P
authors.lastname: Du
authors.affiliation: Department of Colorectal Surgery, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: S
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, No. 270 Dongan Road, Shanghai 200032, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital affiliated to Tongji University School of Life Science and Technology, No. 1239 Siping Road, Shanghai 200092, China.
authors.forename: J
authors.initials: J
authors.lastname: Kang
authors.affiliation: Department of Colorectal Surgery, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: L
authors.initials: L
authors.lastname: Cui
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis
chemical_list: D015820:Cadherins; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D020778:Matrix Metalloproteinase 2