Advertisement

European Journal of Dermatology

, Volume 28, Issue 5, pp 613–620 | Cite as

circCOL3A1-859267 regulates type I collagen expression by sponging miR-29c in human dermal fibroblasts

  • Yating Peng
  • Xiaojing Song
  • Yue Zheng
  • Haiyan Cheng
  • Wei Lai
Investigative report
  • 1 Downloads

Abstract

Background

The genes COL1A1 and COL1A2 encode the pro-alpha 1 and pro-alpha 2 chains of type I collagen, respectively, which is one of the main components of skin dermis.We have previously demonstrated that a circularRNA(a class of recently identified non-codingRNAs that exhibit regulatory potency by sequestering miRNAs like a sponge), which we termed circCOL3A1-859267, is downregulated and regulates type I collagen expression in UVA-exposed human dermal fibroblasts (HDFs). However, the precise mechanisms of circCOL3A1-859267-mediated collagen expression in UVA-irradiated HDFs remain unclear.

Objectives

To elucidate the mechanism of circCOL3A1-859267-mediated regulation of type I collagen expression.

Materials & methods

We initially predicted miRNA binding sites on circCOL3A1-859267 based on a bioinformatic method, and a dual luciferase reporter assay was used to determine miRNA binding to circCOL3A1-859267 in HEK 293 cells. The effect of UVA irradiation on the expression of miRNAs as well as circCOL3A1-859267-mediated type I collagen expression was further investigated in HDFs.

Results

miR-29a, miR-29b, miR-29c, miR-767, and miR-133a were predicted to bind both circCOL3A1-859267 and COL1A1/COL1A2, however, only miR-29c was shown to bind to circCOL3A1-859267 based on the dual luciferase reporter assay. In UVA-exposed HDFs, only miR-29c was upregulated. Finally, transfection of a small interfering RNA targeting circCOL3A1-859267 or miR-29c mimic suppressed the expression of type I collagen in HDFs; the miR-29c mimic-induced down-regulation was restored via overexpression of circCOL3A1-859267 using a lentiviral-based expression system.

Conclusion

Our results indicate that circCOL3A1-859267 regulates type I collagen expression by sponging and sequestering miR-29c in HDFs.

Key words

circRNA miRNA UVA fibroblast collagen 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Yaar M, Gilchrest BA. Photoageing: mechanism, prevention and therapy. Br J Dermatol 2007; 157: 874–87.CrossRefGoogle Scholar
  2. 2.
    Gilchrest BA. Photoaging. J Invest Dermatol 2013; 133: e2–6.CrossRefGoogle Scholar
  3. 3.
    Chung JH, Seo JY, Choi HR, et al. Modulation of skin collagen metabolism in aged and photoaged human skin in vivo. J Invest Dermatol 2001; 117: 1218–24.CrossRefGoogle Scholar
  4. 4.
    Scharffetter–Kochanek K, Brenneisen P, Wenk J, et al. Photoaging of the skin from phenotype to mechanisms. Exp Gerontol 2000; 35: 307–16.CrossRefGoogle Scholar
  5. 5.
    Fisher GJ, Datta S, Wang Z, et al. c–Jun–dependent inhibition of cutaneous procollagen transcription following ultraviolet irradiation is reversed by all–trans retinoic acid. J Clin Invest 2000; 106: 663–70.CrossRefGoogle Scholar
  6. 6.
    Talwar HS, Griffiths CE, Fisher GJ, Hamilton TA, Voorhees JJ. Reduced type I and type III procollagens in photodamaged adult human skin. J Invest Dermatol 1995; 105: 285–90.CrossRefGoogle Scholar
  7. 7.
    Zhang JA, Zhou BR, Xu Y, et al. MiR–23a–depressed autophagy is a participant in PUVA–and UVB–induced premature senescence. Oncotarget 2016; 7: 37420–35.Google Scholar
  8. 8.
    Syed DN, Khan MI, Shabbir M, Mukhtar H. MicroRNAs in skin response to UV radiation. Curr Drug Targets 2013; 14: 1128–34.CrossRefGoogle Scholar
  9. 9.
    Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 2013; 495: 333–8.CrossRefGoogle Scholar
  10. 10.
    Hansen TB, Jensen TI, Clausen BH, et al. Natural RNA circles function as efficient microRNA sponges. Nature 2013; 495: 384–8.CrossRefGoogle Scholar
  11. 11.
    Jeck WR, Sorrentino JA, Wang K, et al. Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA 2013; 19: 141–57.CrossRefGoogle Scholar
  12. 12.
    Wilusz JE, Sharp PA. Molecular biology. A circuitous route to noncoding RNA. Science 2013; 340: 440–1.Google Scholar
  13. 13.
    Du WW, Yang W, Liu E, Yang Z, Dhaliwal P, Yang BB. Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2. Nucleic Acids Res 2016; 44: 2846–58.CrossRefGoogle Scholar
  14. 14.
    Peng Y, Song X, Zheng Y, Wang X, Lai W. Circular RNA profiling reveals that circCOL3A1–859267 regulate type I collagen expression in photoaged human dermal fibroblasts. Biochem Biophys Res Commun 2017; 486: 277–84.CrossRefGoogle Scholar
  15. 15.
    Wang K, Long B, Liu F, et al. A circular RNA protects the heart from pathological hypertrophy and heart failure by targeting miR–223. Eur Heart J 2016; 37: 2602–11.CrossRefGoogle Scholar
  16. 16.
    Wilusz JE. Circular RNAs: unexpected outputs of many proteincoding genes. RNA Biol 2017; 14: 1007–17.CrossRefGoogle Scholar
  17. 17.
    Li Z, Huang C, Bao C, et al. Exon–intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol 2015; 22: 256–64.CrossRefGoogle Scholar
  18. 18.
    Zhang Y, Zhang XO, Chen T, et al. Circular intronic long noncoding RNAs. Mol Cell 2013; 51: 792–806.CrossRefGoogle Scholar
  19. 19.
    Panda AC, Grammatikakis I, Kim KM, et al. Identification of senescence–associated circular RNAs (SAC–RNAs) reveals senescence suppressor CircPVT1. Nucleic Acids Res 2017; 45: 4021–35.CrossRefGoogle Scholar
  20. 20.
    Yang W, Du WW, Li X, Yee AJ, Yang BB. Foxo3 activity promoted by non–coding effects of circular RNA and Foxo3 pseudogene in the inhibition of tumor growth and angiogenesis. Oncogene 2016; 35: 3919–31.CrossRefGoogle Scholar
  21. 21.
    Zheng Q, Bao C, Guo W, et al. Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun 2016; 7: 11215.CrossRefGoogle Scholar
  22. 22.
    Wan L, Zhang L, Fan K, Cheng ZX, Sun QC, Wang JJ. Circular RNA–ITCH suppresses lung cancer proliferation via inhibiting the wnt/beta–catenin pathway. Biomed Res Int 2016; 2016: 1579490.Google Scholar
  23. 23.
    Cushing L, Kuang P, Lu J. The role of miR–29 in pulmonary fibrosis. Biochem Cell Biol 2015; 9: 109–18.CrossRefGoogle Scholar
  24. 24.
    Wang B, Komers R, Carew R, et al. Suppression of microRNA–29 expression by TGF–beta1 promotes collagen expression and renal fibrosis. J Am Soc Nephrol 2012; 23: 252–65.CrossRefGoogle Scholar
  25. 25.
    Roderburg C, Urban GW, Bettermann K, et al. Micro–RNA profiling reveals a role for miR–29 in human and murine liver fibrosis. Hepatology 2011; 53: 209–18.CrossRefGoogle Scholar
  26. 26.
    Harmanci D, Erkan EP, Kocak A, Akdogan GG. Role of the microRNA–29 family in fibrotic skin diseases. Biomed Rep 2017; 6: 599–604.CrossRefGoogle Scholar
  27. 27.
    Peng WJ, Tao JH, Mei B, et al. MicroRNA–29: a potential therapeutic target for systemic sclerosis. Expert Opin Ther Targets 2012; 16: 875–9.CrossRefGoogle Scholar
  28. 28.
    Varani J, Schuger L, Dame MK, et al. Reduced fibroblast interaction with intact collagen as a mechanism for depressed collagen synthesis in photodamaged skin. J Invest Dermatol 2004; 122: 1471–9.CrossRefGoogle Scholar

Copyright information

© John Libbey Eurotext 2018

Authors and Affiliations

  • Yating Peng
    • 1
    • 2
  • Xiaojing Song
    • 1
  • Yue Zheng
    • 1
  • Haiyan Cheng
    • 1
  • Wei Lai
    • 1
  1. 1.Department of Dermatology and VenereologyThird Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina
  2. 2.Department of Dermatology and Venereologythe Second Affiliated Hospital of Nanchang UniversityNanchangChina

Personalised recommendations