Skip to main content
Log in

Identification of microRNAs associated with hyperthermia-induced cellular stress response

  • Short Communication
  • Published:
Cell Stress and Chaperones Aims and scope

Abstract

MicroRNAs (miRNAs) are a class of small RNAs that play a critical role in the coordination of fundamental cellular processes. Recent studies suggest that miRNAs participate in the cellular stress response (CSR), but their specific involvement remains unclear. In this study, we identify a group of thermally regulated miRNAs (TRMs) that are associated with the CSR. Using miRNA microarrays, we show that dermal fibroblasts differentially express 123 miRNAs when exposed to hyperthermia. Interestingly, only 27 of these miRNAs are annotated in the current Sanger registry. We validated the expression of the annotated miRNAs using qPCR techniques, and we found that the qPCR and microarray data was in well agreement. Computational target-prediction studies revealed that putative targets for the TRMs are heat shock proteins and Argonaute-2—the core functional unit of RNA silencing. These results indicate that cells express a specific group of miRNAs when exposed to hyperthermia, and these miRNAs may function in the regulation of the CSR. Future studies will be conducted to determine if other cells lines differentially express these miRNAs when exposed to hyperthermia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

References

  • Ambros V (2001) microRNAs: tiny regulators with great potential. Cell 107(7):823–826

    Article  PubMed  CAS  Google Scholar 

  • Babar IA, Slack FJ et al (2008) miRNA modulation of the cellular stress response. Future Oncol 4(2):289–298

    Article  PubMed  CAS  Google Scholar 

  • Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297

    Article  PubMed  CAS  Google Scholar 

  • Benjamini Y, Drai D et al (2001) Controlling the false discovery rate in behavior genetics research. Behav Brain Res 125(1–2):279–284

    Article  PubMed  CAS  Google Scholar 

  • Bentwich I, Avniel A et al (2005) Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet 37(7):766–770

    Article  PubMed  CAS  Google Scholar 

  • Berezikov E, Guryev V et al (2005) Phylogenetic shadowing and computational identification of human microRNA genes. Cell 120(1):21–24

    Article  PubMed  CAS  Google Scholar 

  • Bhattacharyya SN, Habermacher R et al (2006) Relief of microRNA-mediated translational repression in human cells subjected to stress. Cell 125(6):1111–1124

    Article  PubMed  CAS  Google Scholar 

  • Cimmino A, Calin GA et al (2005) miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA 102(39):13944–13949

    Article  PubMed  CAS  Google Scholar 

  • Cummins JM, He Y et al (2006) The colorectal microRNAome. Proc Natl Acad Sci USA 103(10):3687–3692

    Article  PubMed  CAS  Google Scholar 

  • Deraison C, Bonnart C et al (2007) LEKTI fragments specifically inhibit KLK5, KLK7, and KLK14 and control desquamation through a pH-dependent interaction. Mol Biol Cell 18(9):3607–3619

    Article  PubMed  CAS  Google Scholar 

  • Diller KR (2006) Stress protein expression kinetics. Annu Rev Biomed Eng 8:403–424

    Article  PubMed  CAS  Google Scholar 

  • Feder ME, Hofmann GE (1999) Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiology. Annu Rev Physiol 61:243–282

    Article  PubMed  CAS  Google Scholar 

  • Griffiths-Jones S (2004) The microRNA registry. Nucl Acids Res 32(suppl_1):D109–D111

    Article  PubMed  CAS  Google Scholar 

  • Griffiths-Jones S, Grocock RJ et al (2006) miRBase: microRNA sequences, targets and gene nomenclature. Nucl Acids Res 34(suppl_1):D140–D144

    Article  PubMed  CAS  Google Scholar 

  • Griffiths-Jones S, Saini HK et al (2008) miRBase: tools for microRNA genomics. Nucl Acids Res 36(suppl_1):D154–D158

    PubMed  CAS  Google Scholar 

  • Gu J, Iyer VR (2006) PI3K signaling and miRNA expression during the response of quiescent human fibroblasts to distinct proliferative stimuli. Genome Biol 7(5):R42

    Article  PubMed  CAS  Google Scholar 

  • Hofacker IL (2003) Vienna RNA secondary structure server. Nucleic Acids Res 31(13):3429–3431

    Article  PubMed  CAS  Google Scholar 

  • Izzotti A, Calin GA et al (2009) Downregulation of microRNA expression in the lungs of rats exposed to cigarette smoke. FASEB J 23:806–812

    Article  PubMed  CAS  Google Scholar 

  • Johnson CD, Esquela-Kerscher A et al (2007) The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res 67(16):7713–7722

    Article  PubMed  CAS  Google Scholar 

  • Kabakov AE, Budagova KR et al (2002) Stressful preconditioning and HSP70 overexpression attenuate proteotoxicity of cellular ATP depletion. Am J Physiol Cell Physiol 283(2):C521–C534

    PubMed  CAS  Google Scholar 

  • Kamel S, Kruger C et al (2009) Morpholino-mediated knockdown in primary chondrocytes implicates Hoxc8 in regulation of cell cycle progression. Bone 44(4):708–716

    Article  PubMed  CAS  Google Scholar 

  • Kawasaki H, Taira K (2009) MicroRNA-196 inhibits HOXB8 expression in myeloid differentiation of HL60 cells. Nucleic Acids Symp Ser 2004 48(1):211–212

    Google Scholar 

  • Kertesz M, Iovino N et al (2007) The role of site accessibility in microRNA target recognition. Nat Genet 39(10):1278–1284

    Article  PubMed  CAS  Google Scholar 

  • Kojima R, Randall JD et al (2004) Regulation of expression of the stress response gene, Osp94: identification of the tonicity response element and intracellular signalling pathways. Biochem J 380(Pt 3):783–794

    Article  PubMed  CAS  Google Scholar 

  • Kulshreshtha R, Ferracin M et al (2007) A microRNA signature of hypoxia. Mol Cell Biol 27(5):1859–1867

    Article  PubMed  CAS  Google Scholar 

  • Kultz D (2003) Evolution of the cellular stress proteome: from monophyletic origin to ubiquitous function. J Exp Biol 206(Pt 18):3119–3124

    Article  PubMed  CAS  Google Scholar 

  • Kultz D (2005) Molecular and evolutionary basis of the cellular stress response. Annu Rev Physiol 67:225–257

    Article  PubMed  CAS  Google Scholar 

  • Lee RC, Feinbaum RL et al (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5):843–854

    Article  PubMed  CAS  Google Scholar 

  • Lee DY, Deng Z et al (2007) MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression. Proc Natl Acad Sci USA 104(51):20350–20355

    Article  PubMed  Google Scholar 

  • Leung AK, Sharp PA (2007) microRNAs: a safeguard against turmoil? Cell 130(4):581–585

    Article  PubMed  CAS  Google Scholar 

  • Leung AK, Calabrese JM et al (2006) Quantitative analysis of Argonaute protein reveals microRNA-dependent localization to stress granules. Proc Natl Acad Sci USA 103(48):18125–18130

    Article  PubMed  CAS  Google Scholar 

  • Lewis BP, Shih IH et al (2003) Prediction of mammalian microRNA targets. Cell 115(7):787–798

    Article  PubMed  CAS  Google Scholar 

  • Lewis BP, Burge CB et al (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120(1):15–20

    Article  PubMed  CAS  Google Scholar 

  • Li L-C, Okino ST et al (2008) Small dsRNAs induce transcripitional activation in human cells. PNAS 103(46):17337–17342

    Article  CAS  Google Scholar 

  • Lim LP, Lau NC et al (2003) The microRNAs of Caenorhabditis elegans. Genes Dev 17(8):991–1008

    Article  PubMed  CAS  Google Scholar 

  • Lin YC, Hsieh LC et al (2007) Human TRIM71 and its nematode homologue are targets of let-7 microRNA and its zebrafish orthologue is essential for development. Mol Biol Evol 24(11):2525–2534

    Article  PubMed  CAS  Google Scholar 

  • Marsit CJ, Eddy K et al (2006) MicroRNA responses to cellular stress. Cancer Res 66(22):10843–10848, doi:10.1158/0008-5472.CAN-06-1894

    Article  PubMed  CAS  Google Scholar 

  • Meister G, Landthaler M et al (2004) Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell 15(2):185–197

    Article  PubMed  CAS  Google Scholar 

  • Millenbaugh NJ, Roth C et al (2008) Gene expression changes in the skin of rats induced by prolonged 35 GHz millimeter-wave exposure. Radiat Res 169(3):288–300

    Article  PubMed  CAS  Google Scholar 

  • Miller BA (2006) The role of TRP channels in oxidative stress-induced cell death. J Membr Biol 209(1):31–41

    Article  PubMed  CAS  Google Scholar 

  • Mitomo S, Maesawa C et al (2008) Downregulation of miR-138 is associated with overexpression of human telomerase reverse transcriptase protein in human anaplastic thyroid carcinoma cell lines. Cancer Sci 99(2):280–286

    Article  PubMed  CAS  Google Scholar 

  • Morimoto RI (1993) Cells in stress: transcriptional activation of heat shock genes. Science 259(5100):1409–1410

    Article  PubMed  CAS  Google Scholar 

  • Morimoto RI, Kroeger PE et al (1996) The transcriptional regulation of heat shock genes: a plethora of heat shock factors and regulatory conditions. Exs 77:139–163

    PubMed  CAS  Google Scholar 

  • Moss EG, Lee RC et al (1997) The cold shock domain protein LIN-28 controls developmental timing in C. elegans and is regulated by the lin-4 RNA. Cell 88(5):637–646

    Article  PubMed  CAS  Google Scholar 

  • Papadopoulos GL, Reczko M et al (2009) The database of experimentally supported targets: a functional update of TarBase. Nucleic Acids Res 37(Database issue):D155–D158

    Article  PubMed  CAS  Google Scholar 

  • Park SM, Peter ME (2008) microRNAs and death receptors. Cytokine Growth Factor Rev 19(3–4):303–311

    Article  PubMed  CAS  Google Scholar 

  • Pillai RS, Bhattacharyya SN et al (2007) Repression of protein synthesis by miRNAs: how many mechanisms? Trends Cell Biol 17(3):118–126

    Article  PubMed  CAS  Google Scholar 

  • Place RF, Li LC et al (2008) MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc Natl Acad Sci USA 105(5):1608–1613

    Article  PubMed  Google Scholar 

  • Rajewsky N (2006) microRNA target predictions in animals. Nat Genet 38 Supp:S8–S13

    Article  CAS  Google Scholar 

  • Rougvie AE (2005) Intrinsic and extrinsic regulators of developmental timing: from miRNAs to nutritional cues. Development 132(17):3787–3798

    Article  PubMed  CAS  Google Scholar 

  • Schreck R, Albermann K et al (1992) Nuclear factor kappa B: an oxidative stress-responsive transcription factor of eukaryotic cells (a review). Free Radic Res Commun 17(4):221–237

    Article  PubMed  CAS  Google Scholar 

  • Sethupathy P, Corda B et al (2006) TarBase: a comprehensive database of experimentally supported animal microRNA targets. Rna 12(2):192–197

    Article  PubMed  CAS  Google Scholar 

  • Valencia-Sanchez MA, Liu J et al (2006) Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev 20(5):515–524

    Article  PubMed  CAS  Google Scholar 

  • Vasudevan S, Tong Y et al (2007) Switching from repression to activation: microRNAs can up-regulate translation. Science 318(5858):1931–1934

    Article  PubMed  CAS  Google Scholar 

  • Weidhaas JB, Babar I et al (2007) MicroRNAs as potential agents to alter resistance to cytotoxic anticancer therapy. Cancer Res 67(23):11111–11116

    Article  PubMed  CAS  Google Scholar 

  • White RA, McNulty SG et al (2005) Positional cloning of the Ttc7 gene required for normal iron homeostasis and mutated in hea and fsn anemia mice. Genomics 85(3):330–337

    Article  PubMed  CAS  Google Scholar 

  • Wightman B, Ha I et al (1993) Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75(5):855–862

    Article  PubMed  CAS  Google Scholar 

  • Wilmink GJ, Opalenik SR et al (2006) Assessing laser-tissue damage with bioluminescent imaging. J Biomed Opt 11(4):041114

    Article  PubMed  Google Scholar 

  • Wilmink GJ, Opalenik SR et al (2009) Molecular imaging-assisted optimization of hsp70 expression during laser-induced thermal preconditioning for wound repair enhancement. J Invest Dermatol 129(1):205–216

    Article  PubMed  CAS  Google Scholar 

  • Wu L, Fan J et al (2006) MicroRNAs direct rapid deadenylation of mRNA. Proc Natl Acad Sci USA 103(11):4034–4039

    Article  PubMed  CAS  Google Scholar 

  • Xie X, Lu J et al (2005) Systematic discovery of regulatory motifs in human promoters and 3′ UTRs by comparison of several mammals. Nature 434(7031):338–345

    Article  PubMed  CAS  Google Scholar 

  • Yekta S, Shih IH et al (2004) MicroRNA-directed cleavage of HOXB8 mRNA. Science 304(5670):594–596

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We wish to thank the National Academy of Sciences NRC for providing Dr. Wilmink with a research associateship at the Air Force Research Laboratory. This work was supported by grants provided by HQAF SGRS Clinical Investigation program: “Neurological Impacts of Nanosecond Electric Pulse Exposure” and “Determination of Cellular Bioeffect Thresholds for Terahertz Frequencies.” A special thank-you is also extended to Dr. Susan Opalenik, my eternal lily pad, and Mr. Luisiana X. Cundin.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gerald J. Wilmink.

Additional information

Contract grant sponsor: DOD- SGRS Clinical Investigation program

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wilmink, G.J., Roth, C.L., Ibey, B.L. et al. Identification of microRNAs associated with hyperthermia-induced cellular stress response. Cell Stress and Chaperones 15, 1027–1038 (2010). https://doi.org/10.1007/s12192-010-0189-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12192-010-0189-7

Keywords

Navigation