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Dynamic analysis of DNA damage induced miRNAs in colon cancer cells

  • Article
  • Oncology
  • Published:
Chinese Science Bulletin

Abstract

It is known that microRNAs (miRNAs) expression profile shows substantial changes in cells under DNA damage. Here, we did miRNA microarray and quantitative real-time PCR to comprehensively identify the differentially expressed miRNAs in colon cancer cell lines HCT116 p53+/+ and HCT116 p53−/−. Cluster analysis revealed a panel of differentially expressed miRNAs which are regulated by p53 and/or UV-C induced DNA damage. These altered miRNAs tend to be located in chromosomes 13, X and 17. Moreover, pathways enrichment analysis estimated that MAPK pathway, focal adheren pathway, p53 pathway and Wnt pathway were mediated by these miRNAs to exert their functions in DNA damage response. Additionally, we found that miR-320a, one of the UV-C induced miRNAs, play a role in protecting cells from DNA damage. Taken together, our results show that miRNAs are dynamic regulated in p53-dependent or -independent manners in different cell contexts and different situations following DNA damage.

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References

  1. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233

    Article  Google Scholar 

  2. Bohlig L, Friedrich M, Engeland K (2011) p53 activates the PANK1/miRNA-107 gene leading to downregulation of CDK6 and p130 cell cycle proteins. Nucleic Acids Res 39:440–453

    Article  Google Scholar 

  3. Boominathan L (2010) The tumor suppressors p53, p63, and p73 are regulators of microRNA processing complex. PLoS One 5:e10615

  4. Bronisz A, Godlewski J, Wallace JA et al (2012) Reprogramming of the tumour microenvironment by stromal PTEN-regulated miR-320. Nat Cell Biol 14:159–167

    Article  Google Scholar 

  5. Ciccia A, Elledge SJ (2010) The DNA damage response: making it safe to play with knives. Mol Cell 40:179–204

    Article  Google Scholar 

  6. Gentile M, Latonen L, Laiho M (2003) Cell cycle arrest and apoptosis provoked by UV radiation-induced DNA damage are transcriptionally highly divergent responses. Nucleic Acids Res 31:4779–4790

    Article  Google Scholar 

  7. Harper JW, Elledge SJ (2007) The DNA damage response: ten years after. Mol Cell 28:739–745

    Article  Google Scholar 

  8. He L, He X, Lim LP et al (2007) A microRNA component of the p53 tumour suppressor network. Nature 447:1130–1134

    Article  Google Scholar 

  9. Hermeking H (2012) MicroRNAs in the p53 network: micromanagement of tumour suppression. Nat Rev Cancer 12:613–626

    Article  Google Scholar 

  10. Hoh J, Jin S, Parrado T et al (2002) The p53MH algorithm and its application in detecting p53-responsive genes. Proc Natl Acad Sci USA 99:8467–8472

    Article  Google Scholar 

  11. Hsieh IS, Chang KC, Tsai YT et al (2013) MicroRNA-320 suppresses the stem cell-like characteristics of prostate cancer cells by downregulating the Wnt/beta-catenin signaling pathway. Carcinogenesis 34:530–538

    Article  Google Scholar 

  12. Hu H, Gatti RA (2011) MicroRNAs: new players in the DNA damage response. J Mol Cell Biol 3:151–158

    Article  Google Scholar 

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

    Article  Google Scholar 

  14. Kyriakis JM, Avruch J (2012) Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update. Physiol Rev 92:689–737

    Article  Google Scholar 

  15. Lakin ND, Jackson SP (1999) Regulation of p53 in response to DNA damage. Oncogene 18:7644–7655

    Article  Google Scholar 

  16. Leung AK, Sharp PA (2010) MicroRNA functions in stress responses. Mol Cell 40:205–215

    Article  Google Scholar 

  17. Leveille N, Elkon R, Davalos V et al (2011) Selective inhibition of microRNA accessibility by RBM38 is required for p53 activity. Nat Commun 2:513

    Article  Google Scholar 

  18. Lindahl T, Barnes DE (2000) Repair of endogenous DNA damage. Cold Spring Harb Symp Quant Biol 65:127–133

    Article  Google Scholar 

  19. Lu TP, Lee CY, Tsai MH et al (2012) miRSystem: an integrated system for characterizing enriched functions and pathways of microRNA targets. PLoS One 7:e42390

  20. Manke IA, Nguyen A, Lim D et al (2005) MAPKAP kinase-2 is a Cell cycle checkpoint kinase that regulates the G2M transition and S phase progression in response to UV irradiation. Mol Cell 17:37–48

  21. Roche KC, Rocha S, Bracken CP et al (2007) Regulation of ATR-dependent pathways by the FHA domain containing protein SNIP1. Oncogene 26:4523–4530

    Article  Google Scholar 

  22. Rodriguez A, Griffiths-Jones S, Ashurst JL et al (2004) Identification of mammalian microRNA host genes and transcription units. Genome Res 14:1902–1910

    Article  Google Scholar 

  23. Schaar DG, Medina DJ, Moore DF et al (2009) miR-320 targets transferrin receptor 1 (CD71) and inhibits cell proliferation. Exp Hematol 37:245–255

    Article  Google Scholar 

  24. Seker H, Rubbi C, Linke SP et al (2003) UV-C-induced DNA damage leads to p53-dependent nuclear trafficking of PML. Oncogene 22:1620–1628

    Article  Google Scholar 

  25. Shimono Y, Zabala M, Cho RW et al (2009) Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell 138:592–603

    Article  Google Scholar 

  26. Smith RA, Brooks D, Cokkinides V et al (2013) Cancer screening in the United States, 2013: a review of current American Cancer Society guidelines, current issues in cancer screening, and new guidance on cervical cancer screening and lung cancer screening. CA Cancer J Clin 63:88–105

    Article  Google Scholar 

  27. Sun JY, Huang Y, Li JP et al (2012) MicroRNA-320a suppresses human colon cancer cell proliferation by directly targeting beta-catenin. Biochem Biophys Res Commun 420:787–792

    Article  Google Scholar 

  28. Suzuki HI, Yamagata K, Sugimoto K et al (2009) Modulation of microRNA processing by p53. Nature 460:529–533

    Article  Google Scholar 

  29. Trabucchi M, Briata P, Garcia-Mayoral M et al (2009) The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs. Nature 459:1010–1014

    Article  Google Scholar 

  30. Wu CW, Dong YJ, Liang QY et al (2013) MicroRNA-18a attenuates DNA damage repair through suppressing the expression of ataxia telangiectasia mutated in colorectal cancer. PLoS One 8:e57036

  31. Xu N, Papagiannakopoulos T, Pan G et al (2009) MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell 137:647–658

    Article  Google Scholar 

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81021061). We appreciated Xuefeng Liu, Yunwei Ou and Jia Li for revising this manuscript and offering constructive advices.

Conflict of interests

The authors declare no conflict of interest.

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Authors and Affiliations

  1. State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

    Weimin Zhang, Fang Yang & Qimin Zhan

  2. Sir Run Run Shaw Hospital (SRRSH), Zhejiang University School of Medicine, Hangzhou, 310016, China

    Fang Yang

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  1. Weimin Zhang
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  2. Fang Yang
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  3. Qimin Zhan
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Correspondence to Qimin Zhan.

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SPECIAL TOPIC: MicroRNA and Tumor

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Zhang, W., Yang, F. & Zhan, Q. Dynamic analysis of DNA damage induced miRNAs in colon cancer cells. Chin. Sci. Bull. 59, 2254–2265 (2014). https://doi.org/10.1007/s11434-014-0331-5

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  • DOI: https://doi.org/10.1007/s11434-014-0331-5

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