title: Role of microRNAs in regulation of the TNF/TNFR gene superfamily in chronic lymphocytic leukemia.
abstract: BACKGROUND
  Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. The biology of this disease remains elusive. In the present times, targeted molecular therapy defines the treatment. This has made understanding the elusive biology and molecular mechanisms of the disease more relevant. MicroRNAs (miRNAs) are non-encoding RNAs that play important gene-regulatory roles in neoplastic processes. As in silico studies list nearly hundreds and more target genes for each miRNA, it is of interest to see if there are genes that have already been implicated in this disease.
  
  
  OBJECTIVE
  The purpose of this study was to identify genes regulated by miRNAs that are independently implicated in the pathogenesis of CLL in previously published literature.
  
  
  METHODS
  Eight miRNAs were selected. Genes implicated in the biology of CLL in association studies and massively parallel sequence studies were selected. TargetScanHuman 6.2, a computational program that predicts target genes of miRNAs on the basis of sequence analysis, was used to link the miRNAs to genes of interest.
  
  
  RESULTS
  The genes targeted by miR-15a, miR-223, miR-29a, and miR181a included IL10RA, BCL2, BCL6, DDX3X, and FBXW7. The most significant link observed was that several gene members of the TNF/TNFR superfamily were targets of miR-15a, miR-29a, and miR-181a.
  
  
  CONCLUSIONS
  MiRNAs implicated in the pathogenesis of CLL regulate genes that have independently been shown to play a role in CLL. The link between miRNAs and the TNF/TNFR superfamily is especially exciting. Understanding the molecular basis of these links in future studies may pave the way for using these miRNAs as therapeutic targets in CLL.
authors.affiliation: Department of Pathology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA; Department of Pathology, Dartmouth Hitchcock Medical Center, Norris Cotton Cancer Center, Lebanon, NH 03756, USA.
authors.forename: Swati
authors.initials: S
authors.lastname: Srivastava
authors.affiliation: Department of Pathology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA; Department of Pathology, Dartmouth Hitchcock Medical Center, Norris Cotton Cancer Center, Lebanon, NH 03756, USA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Tsongalis
authors.affiliation: Department of Pathology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA; Department of Pathology, Dartmouth Hitchcock Medical Center, Norris Cotton Cancer Center, Lebanon, NH 03756, USA. Electronic address: Prabhjot.Kaur@Hitchcock.org.
authors.forename: Prabhjot
authors.initials: P
authors.lastname: Kaur
mesh_terms: D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell; D035683:MicroRNAs / Q000502:physiology*; D005810:Multigene Family; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha
keywords: CLL; MiRNA; TNF