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  • Chavali, SreenivasMRC Laboratory of Molecular Biology, Cambridge, United Kingdom (author)

MicroRNAs act complementarily to regulate disease-related mRNA modules in human diseases

  • Article/chapterEnglish2013

Publisher, publication year, extent ...

  • 2013-09-23
  • Cold Spring Harbor Laboratory,2013
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/186269
  • https://gup.ub.gu.se/publication/186269URI
  • https://doi.org/10.1261/rna.038414.113DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-99867URI

Supplementary language notes

  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • MicroRNAs (miRNAs) play a key role in regulating mRNA expression, and individual miRNAs have been proposed as diagnostic and therapeutic candidates. The identification of such candidates is complicated by the involvement of multiple miRNAs and mRNAs as well as unknown disease topology of the miRNAs. Here, we investigated if disease-associated miRNAs regulate modules of disease-associated mRNAs, if those miRNAs act complementarily or synergistically, and if single or combinations of miRNAs can be targeted to alter module functions. We first analyzed publicly available miRNA and mRNA expression data for five different diseases. Integrated target prediction and network-based analysis showed that the miRNAs regulated modules of disease-relevant genes. Most of the miRNAs acted complementarily to regulate multiple mRNAs. To functionally test these findings, we repeated the analysis using our own miRNA and mRNA expression data from CD4+ T cells from patients with seasonal allergic rhinitis. This is a good model of complex diseases because of its well-defined phenotype and pathogenesis. Combined computational and functional studies confirmed that miRNAs mainly acted complementarily and that a combination of two complementary miRNAs, miR-223 and miR-139-3p, could be targeted to alter disease-relevant module functions, namely, the release of type 2 helper T-cell (Th2) cytokines. Taken together, our findings indicate that miRNAs act complementarily to regulate modules of disease-related mRNAs and can be targeted to alter disease-relevant functions.

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  • Bruhn, SörenLinköpings universitet,Avdelningen för kliniska vetenskaper,Hälsouniversitetet(Swepub:liu)sorbr27 (author)
  • Tiemann, KatrinLinköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet(Swepub:liu)katti04 (author)
  • Saetrom, P.Norwegian University of Science and Technology, Trondheim, Norway (author)
  • Barrenäs, Fredrik,1981Linköpings universitet,Avdelningen för kliniska vetenskaper,Hälsouniversitetet(Swepub:liu)freba19 (author)
  • Saito, T.Norwegian University of Science and Technology, Trondheim, Norway (author)
  • Kanduri, Kartiek,1986Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics,University of Gothenburg, Sweden(Swepub:gu)xkanka (author)
  • Wang, HuiLinköpings universitet,Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics,Avdelningen för kliniska vetenskaper,Hälsouniversitetet(Swepub:liu)huiwa84 (author)
  • Benson, Mikael,1954Linköpings universitet,Avdelningen för kliniska vetenskaper,Hälsouniversitetet(Swepub:liu)mikbe05 (author)
  • MRC Laboratory of Molecular Biology, Cambridge, United KingdomAvdelningen för kliniska vetenskaper (creator_code:org_t)

Related titles

  • In:Rna-a Publication of the Rna Society: Cold Spring Harbor Laboratory19:11, s. 1552-15621355-83821469-9001
  • In:RNA: Cold Spring Harbor Laboratory19:11, s. 1552-15621469-9001

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