Skip to main content
SpringerLink
Log in

miR-617 Promotes the Growth of IL-22-Stimulated Keratinocytes Through Regulating FOXO4 Expression

  • Original Article
  • Published:
Biochemical Genetics Aims and scope Submit manuscript

Abstract

Psoriasis is considered as a common chronic and relapsing inflammatory skin disease. MicroRNAs (miRNAs) were found to be related with psoriasis pathogenesis. Nevertheless, the function of miR-617 in psoriasis is still unclear. The miR-617 RNA level was detected using quantitative reverse transcription-PCR (qRT-PCR). Western blot analysis examined the protein level. Cell proliferation was analyzed via cell counting kit-8 (CCK-8) assay. Flow cytometry analysis detected cell cycle and apoptosis. The relationship between miR-617 and forkhead box protein O4 (FOXO4) was confirmed through dual luciferase assay. The miR-617 was up-regulated in psoriatic skin tissues and interleukin-22 (IL-22)-stimulated immortalized human keratinocyte HaCaT cells. Moreover, miR-617 mimics promoted proliferation, cell cycle, and suppressed apoptosis in IL-22-stimulated HaCaT cells. However, miR-617 inhibitor showed opposite effects. Additionally, FOXO4 was a target of miR-617. FOXO4 was down-regulated in psoriatic skin tissues and IL-22-stimulated HaCaT cells. Negative correlation between miR-617 and FOXO4 was identified. FOXO4 overexpression alleviated the effects of miR-617 proliferation, cell cycle and apoptosis in the IL-22-stimulated HaCaT cells. These results demonstrate that miR-617 increases the growth of IL-22-stimulated keratinocytes through targeting FOXO4, which provides a new therapeutic target for psoriasis.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

All data generated or analyzed during this study are included in this published article.

References

  • Boehncke WH, Schon MP (2015) Psoriasis. Lancet 386(9997):983–994

    Article  CAS  PubMed  Google Scholar 

  • Bracken CP, Scott HS, Goodall GJ (2016) A network-biology perspective of microRNA function and dysfunction in cancer. Nat Rev Genet 17(12):719–732

    Article  CAS  PubMed  Google Scholar 

  • Capon F (2017) The genetic basis of psoriasis. Int J Mol Sci. 18(12):2526

    Article  PubMed Central  CAS  Google Scholar 

  • Chandra A, Ray A, Senapati S et al (2015) Genetic and epigenetic basis of psoriasis pathogenesis. Mol Immunol 64(2):313–323

    Article  CAS  PubMed  Google Scholar 

  • Chen L, Tang Y, Wang J et al (2013) miR-421 induces cell proliferation and apoptosis resistance in human nasopharyngeal carcinoma via downregulation of FOXO4. Biochem Biophys Res Commun 435(4):745–750

    Article  CAS  PubMed  Google Scholar 

  • Cheng H, Xu M, Liu X et al (2016) TWEAK/Fn14 activation induces keratinocyte proliferation under psoriatic inflammation. Exp Dermatol 25(1):32–37

    Article  CAS  PubMed  Google Scholar 

  • Ding X, Duan H, Luo H (2020) Identification of core gene expression signature and key pathways in colorectal cancer. Front Genet 11:45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eyerich S, Eyerich K, Pennino D et al (2009) Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling. J Clin Invest 119(12):3573–3585

    CAS  PubMed  PubMed Central  Google Scholar 

  • Feng S, Wang L, Liu W et al (2018) MiR-126 correlates with increased disease severity and promotes keratinocytes proliferation and inflammation while suppresses cells' apoptosis in psoriasis. J Clin Lab Anal 32(9):e22588

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Geller S, Xu H, Lebwohl M et al (2018) Malignancy risk and recurrence with psoriasis and its treatments: a concise update. Am J Clin Dermatol 19(3):363–375

    Article  PubMed  PubMed Central  Google Scholar 

  • Hao JQ (2014) Targeting interleukin-22 in psoriasis. Inflammation 37(1):94–99

    Article  CAS  PubMed  Google Scholar 

  • Hawkes JE, Nguyen GH, Fujita M et al (2016) microRNAs in psoriasis. J Invest Dermatol 136(2):365–371

    Article  CAS  PubMed  Google Scholar 

  • Huang H, Tindall DJ (2007) Dynamic FoxO transcription factors. J Cell Sci 120(Pt 15):2479–2487

    Article  CAS  PubMed  Google Scholar 

  • Ji Y, Wang D, Zhang B et al (2019) MiR-361-3p inhibits beta-amyloid accumulation and attenuates cognitive deficits through targeting BACE1 in Alzheimer's disease. J Integr Neurosci 18(3):285–291

    Article  PubMed  Google Scholar 

  • Katoh M, Igarashi M, Fukuda H et al (2013) Cancer genetics and genomics of human FOX family genes. Cancer Lett 328(2):198–206

    Article  CAS  PubMed  Google Scholar 

  • Li J, Hu L, Tian C et al (2015) microRNA-150 promotes cervical cancer cell growth and survival by targeting FOXO4. BMC Mol Biol 16:24

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li H, Ouyang R, Wang Z et al (2016) MiR-150 promotes cellular metastasis in non-small cell lung cancer by targeting FOXO4. Sci Rep 6:39001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liakou AI, Zouboulis CC (2015) Links and risks associated with psoriasis and metabolic syndrome. Psoriasis (Auckl) 5:125–128

    CAS  Google Scholar 

  • Liu Q, Wu DH, Han L et al (2017) Roles of microRNAs in psoriasis: Immunological functions and potential biomarkers. Exp Dermatol 26(4):359–367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu X, Zhang Z, Sun L et al (2011) MicroRNA-499-5p promotes cellular invasion and tumor metastasis in colorectal cancer by targeting FOXO4 and PDCD4. Carcinogenesis 32(12):1798–1805

    Article  CAS  PubMed  Google Scholar 

  • Lovendorf MB, Zibert JR, Gyldenlove M et al (2014) MicroRNA-223 and miR-143 are important systemic biomarkers for disease activity in psoriasis. J Dermatol Sci 75(2):133–139

    Article  PubMed  CAS  Google Scholar 

  • Meisgen F, Xu N, Wei T et al (2012) MiR-21 is up-regulated in psoriasis and suppresses T cell apoptosis. Exp Dermatol 21(4):312–314

    Article  CAS  PubMed  Google Scholar 

  • Otsuka K, Ochiya T (2014) Genetic networks lead and follow tumor development: microRNA regulation of cell cycle and apoptosis in the p53 pathways. Biomed Res Int 2014:749724

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Parisi R, Symmons DP, Griffiths CE et al (2013) Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol 133(2):377–385

    Article  CAS  PubMed  Google Scholar 

  • Riffo-Campos AL, Riquelme I, Brebi-Mieville P (2016) Tools for sequence-based miRNA target prediction: what to choose? Int J Mol Sci 17(12):1987

    Article  PubMed Central  CAS  Google Scholar 

  • Ritchlin CT, Colbert RA, Gladman DD (2017) Psoriatic arthritis. N Engl J Med 376(10):957–970

    Article  PubMed  Google Scholar 

  • Rongna A, Yu P, Hao S et al (2018) MiR-876-5p suppresses cell proliferation by targeting Angiopoietin-1 in the psoriasis. Biomed Pharmacother. 103:1163–1169

    Article  CAS  Google Scholar 

  • Roubille C, Richer V, Starnino T et al (2015) The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis. Ann Rheum Dis 74(3):480–489

    Article  CAS  PubMed  Google Scholar 

  • Shen H, Tian Y, Yao X et al (2017) MiR-99a inhibits keratinocyte proliferation by targeting Frizzled-5 (FZD5) / FZD8 through beta-catenin signaling in psoriasis. Pharmazie 72(8):461–467

    CAS  PubMed  Google Scholar 

  • Shenoy A, Blelloch RH (2014) Regulation of microRNA function in somatic stem cell proliferation and differentiation. Nat Rev Mol Cell Biol 15(9):565–576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shukla GC, Singh J, Barik S (2011) MicroRNAs: Processing, Maturation, Target Recognition and Regulatory Functions. Mol Cell Pharmacol 3(3):83–92

    CAS  PubMed  PubMed Central  Google Scholar 

  • Soonthornchai W, Tangtanatakul P, Meephansan J et al (2019) Down-regulation of miR-155 after treatment with narrow-band UVB and methotrexate associates with apoptosis of keratinocytes in psoriasis. Asian Pac J Allergy Immunol. https://doi.org/10.12932/AP-031218-0451

    Article  Google Scholar 

  • Sun Y, Zhang J, Zhou Z et al (2015) CCN1, a pro-inflammatory factor, aggravates psoriasis skin lesions by promoting keratinocyte activation. J Invest Dermatol 135(11):2666–2675

    Article  CAS  PubMed  Google Scholar 

  • Vide J, Magina S (2017) Moderate to severe psoriasis treatment challenges through the era of biological drugs. An Bras Dermatol 92(5):668–674

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang R, Wang FF, Cao HW et al (2019a) MiR-223 regulates proliferation and apoptosis of IL-22-stimulated HaCat human keratinocyte cell lines via the PTEN/Akt pathway. Life Sci 230:28–34

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Yu X, Wang L et al (2018) miR-320b is down-regulated in psoriasis and modulates keratinocyte proliferation by targeting AKT3. Inflammation 41(6):2160–2170

    Article  CAS  PubMed  Google Scholar 

  • Wang C, Zong J, Li Y et al (2019b) MiR-744-3p regulates keratinocyte proliferation and differentiation via targeting KLLN in psoriasis. Exp Dermatol 28(3):283–291

    Article  CAS  PubMed  Google Scholar 

  • Wawrzycki B, Pietrzak A, Grywalska E et al (2019) Interleukin-22 and its correlation with disease activity in plaque psoriasis. Arch Immunol Ther Exp (Warsz) 67(2):103–108

    Article  CAS  Google Scholar 

  • Zai W, Chen W, Wu Z et al (2019) Targeted interleukin-22 gene delivery in the liver by polymetformin and penetratin-based hybrid nanoparticles to treat nonalcoholic fatty liver disease. ACS Appl Mater Interfaces 11(5):4842–4857

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Tu C, Zhang D et al (2015) Wnt/beta-catenin and Wnt5a/Ca pathways regulate proliferation and apoptosis of keratinocytes in psoriasis lesions. Cell Physiol Biochem 36(5):1890–1902

    Article  CAS  PubMed  Google Scholar 

  • Zhao X, Li R, Qiao M et al (2018) MiR-548a-3p promotes keratinocyte proliferation targeting PPP3R1 after being induced by IL-22. Inflammation 41(2):496–504

    Article  CAS  PubMed  Google Scholar 

  • Zhao L, Lu X, Cao Y (2013) MicroRNA and signal transduction pathways in tumor radiation response. Cell Signal 25(7):1625–1634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu H, Hou L, Liu J et al (2016) MiR-217 is down-regulated in psoriasis and promotes keratinocyte differentiation via targeting GRHL2. Biochem Biophys Res Commun 471(1):169–176

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

This work was supported by Scientific research fund support program of Southwest Medical University of Sichuan Province.

Author information

Authors and Affiliations

  1. Department of Dermatology, The Affiliated Hospital of Southwest Medical University, No. 25 of Taiping Road, Luzhou, 646000, Sichuan, China

    Tao Liu & Yongmei Liao

  2. Department of Ophthalmology, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China

    Xiaomei Feng

Authors
  1. Tao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaomei Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yongmei Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

TL conceived and designed the experiments, XMF analyzed and interpreted the results of the experiments, YML performed the experiments.

Corresponding author

Correspondence to Tao Liu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

The animal experimental processes were performed in accordance with World Medical Association Declaration of Helsinki and approved by Clinical Trial Ethics Committee of the Affiliated Hospital of Southwest Medical University.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

10528_2020_9997_MOESM1_ESM.jpg

Fig.S1. (A) IL-22R expression was measured in the IL-22-stimulated HaCaT cells (n=3) using qRT-PCR. (B) Western blot analysis was performed to confirm the p27 protein level. n=3. **, p<0.01. (364 kB)

Fig.S2. CCK-8 assay measured proliferation in HaCaT cells treated with IL-22. n=3. **p<0.01. (240 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, T., Feng, X. & Liao, Y. miR-617 Promotes the Growth of IL-22-Stimulated Keratinocytes Through Regulating FOXO4 Expression. Biochem Genet 59, 547–559 (2021). https://doi.org/10.1007/s10528-020-09997-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10528-020-09997-4

Keywords

Search

Navigation