title: Identification of biological targets of therapeutic intervention for clear cell renal cell carcinoma based on bioinformatics approach.
abstract: BACKGROUND
  We aimed to discover the potential microRNA (miRNA) targets and to explore the underlying molecular mechanisms of clear cell renal cell carcinoma (ccRCC).
  
  
  METHODS
  Microarray data of GSE16441 was downloaded from Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially expressed miRNAs between ccRCC tumors and matched non-tumor samples were analyzed. Target genes of differentially expressed miRNAs were screened. Besides, functional enrichment analysis of DEGs was performed, followed by protein-protein interaction (PPI) network construction and sub-module analysis. Finally, the integrated miRNA-DEGs network was constructed.
  
  
  RESULTS
  A total of 1758 up- and 2465 down-regulated DEGs were identified. Moreover, 15 up- and 12 down-regulated differentially expressed miRNAs were screened. The up-regulated DEGs were significantly enriched in pathways such as cell adhesion molecules and focal adhesion. Besides, the down-regulated DEGs were enriched in oxidative phosphorylation, and citrate cycle (TCA cycle). Moreover, eight sub-modules of PPI network were obtained. Totally, eight down-regulated miRNAs were identified to significantly regulate the DEGs and miRNA-200c that could regulate collagen, type V, alpha 2 (COL5A2) as well as COL5A3 was found to be the most significant. Additionally, 10 up-regulated miRNAs were identified to be significantly associated with the DEGs. Thereinto, miRNA-15a that could regulate ATPase, H(+) transporting, lysosomal 21 kDa, V0 subunit b (ATP6V0B) and miRNA-155 were found to be the most significant.
  
  
  CONCLUSIONS
  miRNA-200c that could regulate COL5A2 and COL5A3, miRNA-15a that could regulate ATP6V0B and miRNA-155 may play key roles in ccRCC progression. These miRNAs may be potential targets for ccRCC treatment.
authors.affiliation: Department of Urology, Harbin Medical University Cancer Hospital, Harbin, 150040 Heilongjiang Province China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Urology, Harbin Medical University Cancer Hospital, Harbin, 150040 Heilongjiang Province China.
authors.forename: Lichen
authors.initials: L
authors.lastname: Teng
authors.affiliation: Intensive Care Unit (ICU) Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086 Province Heilongjiang China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Urology, Harbin Medical University Cancer Hospital, Harbin, 150040 Heilongjiang Province China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Urology, Harbin Medical University Cancer Hospital, Harbin, 150040 Heilongjiang Province China.
authors.forename: Dexin
authors.initials: D
authors.lastname: Ding
authors.affiliation: Department of Urology, Harbin Medical University Cancer Hospital, Harbin, 150040 Heilongjiang Province China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Urology, Harbin Medical University Cancer Hospital, Harbin, 150040 Heilongjiang Province China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Urology, Harbin Medical University Cancer Hospital, Harbin, 150040 Heilongjiang Province China.
authors.forename: Changfu
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Urology, The First Affiliated Hospital of Harbin Medical University, No.31 Youzheng Street, Harbin, 150001 Province Heilongjiang China.
authors.forename: Ruihua
authors.initials: R
authors.lastname: An
keywords: Clear cell renal cell carcinoma; Differentially expressed genes; MicroRNAs; Protein–protein interaction