title: Identifying Ki-67 specific miRNA-mRNA interactions in malignant astrocytomas.
abstract: BACKGROUND
  Ki-67 is an excellent indicator of glioma cell growth. However, limited information is available regarding the mechanisms underlying abnormal expression of Ki-67 in glioma tissue. The aim of this study is to identify Ki-67 specific miRNA-mRNA interactions on basis of miRNA and mRNA expression profilings.
  
  
  METHODS
  We performed a large-scale miRNA (n=829) and mRNA (n=29,421) expression profiling in primary glioblastoma multiforme (pGBM) and anaplastic astrocytoma (AA) tissues (with an aim to investigate Ki-67 related miRNAs and mRNAs). From target prediction databases, the targeting relationships between Ki-67 specific miRNAs and mRNAs were established, and functions of these mRNAs were analyzed by DAVID. The functional verifications of the candidate miRNA were also performed in LN229 cell line.
  
  
  RESULTS
  High expression level of Ki-67 protein predicted a shorter survival time for patients with AA. Integrated analysis of profiling data from pGBM and AA revealed 4 Ki-67 positively and 5 negatively correlated miRNAs, along with the top 12 Ki-67 positively and 2 negatively correlated mRNAs. By means of target prediction, we found that the target mRNAs employed by miR-218 were the most significant among Ki-67 specific mRNAs. Up-regulation of miR-218 was further demonstrated to reduce Ki-67 expression, promote apoptosis, and induce G0/G1 phase cell cycle arrest in LN229 cells.
  
  
  CONCLUSIONS
  Ki-67 protein may be regulated by specific miRNA-mRNA interactions which may contribute to the proliferation of glioma cells.
authors: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors: Yanwei
authors: Y
authors: Liu
authors: Kai
authors: K
authors: Tang
authors: Wei
authors: W
authors: Yan
authors: Yongzhi
authors: Y
authors: Wang
authors: Gan
authors: G
authors: You
authors: Chunsheng
authors: C
authors: Kang
authors: Tao
authors: T
authors: Jiang
authors: Wei
authors: W
authors: Zhang
mesh_terms: D017209:Apoptosis; D001254:Astrocytoma / Q000473:pathology* / Q000503:physiopathology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D019394:Ki-67 Antigen; D012333:RNA, Messenger