title: MiR-429 up-regulation induces apoptosis and suppresses invasion by targeting Bcl-2 and SP-1 in esophageal carcinoma.
abstract: OBJECTIVE
  MicroRNAs (miRNAs) may act as oncogenes or tumor suppressor genes and, as such, they may play a role in cancer development. We investigated miR-429 expression levels in a cohort of esophageal carcinomas (EC) to assess its impact on EC cell growth, apoptosis and invasion.
  
  
  METHODS
  qRT-PCR assays were used to quantify miR-429 expression levels in 32 paired EC samples and adjacent non-neoplastic tissues. Assays for cell growth, apoptosis, caspase activity and trans-well invasion were used to evaluate the effects of miR-429 expression on EC cells. Luciferase reporter and Western blotting assays were used to test whether the Bcl-2 and specificity protein 1 (SP1) mRNAs serve as major targets of miR-429.
  
  
  RESULTS
  The expression levels of miR-429 in EC tissues were found to be lower than those in adjacent non-neoplastic tissues (P < 0.05). This relatively low expression was found to be significantly associated with the occurrence of lymph node metastases (P < 0.05). Apoptosis and migration rates were found to be significantly higher in two EC-derived cell lines (EC9706 and KYSE30) transfected with a miR-429 agomir (P < 0.05). Subsequent Western blotting and luciferase reporter assays showed that miR-429 can bind to putative binding sites within the Bcl-2 and SP1 mRNA 3' untranslated regions (UTRs) to reduce their expression.
  
  
  CONCLUSIONS
  In primary EC tissues miR-429 is expressed at low levels. Up-regulation of miR-429 inhibits invasion and promotes apoptosis in EC cells by targeting Bcl-2 and SP1. Our findings suggest that Bcl-2 and SP1 may serve as major targets of miR-429. This study paves the way for a better understanding of the mechanism underlying EC pathogenesis and the development of novel, targeted therapies.
authors.affiliation: Department of Microbiology and Immunology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan Province, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Wenqiao
authors.initials: W
authors.lastname: Zang
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Ma
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Zhao
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C546363:MIRN429 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D016329:Sp1 Transcription Factor