Skip to main content

Advertisement

Log in

Human umbilical cord mesenchymal stem cells-derived exosomal microRNA-181a retards nasopharyngeal carcinoma development by mediating KDM5C

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Objective

It has been studied that mesenchymal stem cells (MSCs)-derived exosomes could suppress tumor growth in nasopharyngeal carcinoma (NPC) and microRNA-181a (miR-181a) could mediate drug resistance in NPC. Focused on this work, the mechanism of human umbilical cord MSCs (hUC-MSCs)-derived exosomal miR-181a was explored in NPC cell progression.

Methods

NPC tissues and normal tissues were obtained from patients, and miR-181a and KDM5C expression was examined. hUC-MSCs-derived exosomes were extracted, identified and co-cultured with NPC cells (C666-1 and SUNE1). C666-1 cell progression in vitro and/or tumor growth in vivo were examined after incubation with exosomes, miR-181a or lysine-specific demethylase 5C (KDM5C). miR-181a and KDM5C expression were examined in NPC.

Results

miR-181a expression was reduced while KDM5C expression was elevated in NPC. hUC-MSCs-derived exosomes restrained NPC cell growth in vivo and in vitro. Depleting or restoring exosomal miR-181a promoted or delayed NPC cell progression. KDM5C silencing suppressed NPC cell progression.

Conclusion

This study concluded that hUC-MSCs-derived exosomal miR-181a retards NPC development via negatively modulating KDM5C, serving as a candidate reference for the therapy of NPC.

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
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Chan LS et al (2020) Role of miR-96/EVI1/miR-449a axis in the nasopharyngeal carcinoma cell migration and tumor sphere formation. Int J Mol Sci 21(15):5495

    Article  CAS  Google Scholar 

  • Dai Y et al (2019) miR-181a and miR-203 inhibit migration and invasion of laryngeal carcinoma cells by interacting with ATF2. Int J Clin Exp Pathol 12(1):133–141

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ding Y et al (2019) Exosomes derived from human umbilical cord mesenchymal stromal cells deliver exogenous miR-145-5p to inhibit pancreatic ductal adenocarcinoma progression. Cancer Lett 442:351–361

    Article  CAS  Google Scholar 

  • Duan HG et al (2015) Human umbilical cord mesenchymal stem cells alleviate nasal mucosa radiation damage in a guinea pig model. J Cell Biochem 116(2):331–338

    Article  CAS  Google Scholar 

  • Fu X et al (2020) Effects of cryopreservation and long-term culture on biological characteristics and proteomic profiles of human umbilical cord-derived mesenchymal stem cells. Clin Proteomics 17:15

    Article  CAS  Google Scholar 

  • Hao YR et al (2019) Long non-coding RNA ANRIL promotes proliferation, clonogenicity, invasion and migration of laryngeal squamous cell carcinoma by regulating miR-181a/Snai2 axis. Regen Ther 11:282–289

    Article  Google Scholar 

  • He Z et al (2020) Human umbilical cord mesenchymal stem cells-derived exosomes deliver microRNA-375 to downregulate ENAH and thus retard esophageal squamous cell carcinoma progression. J Exp Clin Cancer Res 39(1):140

    Article  CAS  Google Scholar 

  • Hong Z et al (2019) KDM5C is transcriptionally regulated by BRD4 and promotes castration-resistance prostate cancer cell proliferation by repressing PTEN. Biomed Pharmacother 114:108793

    Article  CAS  Google Scholar 

  • Hu J et al (2020) Human umbilical cord mesenchymal stem cell-derived exosomes suppress dermal fibroblasts-myofibroblats transition via inhibiting the TGF-beta1/Smad 2/3 signaling pathway. Exp Mol Pathol 115:104468

    Article  CAS  Google Scholar 

  • Huq S et al (2020) Repurposing the FDA-approved antiviral drug ribavirin as targeted therapy for nasopharyngeal carcinoma. Mol Cancer Ther 19(9):1797–1808

    Article  CAS  Google Scholar 

  • Ji X et al (2015) Lysine-specific demethylase 5C promotes hepatocellular carcinoma cell invasion through inhibition BMP7 expression. BMC Cancer 15:801

    Article  Google Scholar 

  • Jiang J et al (2019) miR-153-3p suppresses inhibitor of growth protein 2 expression to function as tumor suppressor in acute lymphoblastic leukemia. Technol Cancer Res Treat 18:1533033819852990

    Article  CAS  Google Scholar 

  • Li W et al (2020) A novel nomogram to predict survival in patients with recurrent nasopharyngeal carcinoma after salvage endoscopic surgery. Oral Oncol 111:104922

    Article  Google Scholar 

  • Liu Y et al (2018) Exosomes from mesenchymal stromal cells enhance imatinib-induced apoptosis in human leukemia cells via activation of caspase signaling pathway. Cytotherapy 20(2):181–188

    Article  CAS  Google Scholar 

  • Lv B et al (2020) The tumor-suppressive role of microRNA-873 in nasopharyngeal carcinoma correlates with downregulation of ZIC2 and inhibition of AKT signaling pathway. Cancer Gene Ther 28:74

    Article  Google Scholar 

  • Mao W et al (2019) Circular RNA hsa_circ_0068871 regulates FGFR3 expression and activates STAT3 by targeting miR-181a-5p to promote bladder cancer progression. J Exp Clin Cancer Res 38(1):169

    Article  Google Scholar 

  • Qiu L et al (2020) Exosomal microRNA146a derived from mesenchymal stem cells increases the sensitivity of ovarian cancer cells to docetaxel and taxane via a LAMC2mediated PI3K/Akt axis. Int J Mol Med 46(2):609–620

    Article  CAS  Google Scholar 

  • Shen H et al (2016) Suppression of enhancer overactivation by a RACK7-histone demethylase complex. Cell 165(2):331–342

    Article  CAS  Google Scholar 

  • Shi Q et al (2017) MiR-181a inhibits non-small cell lung cancer cell proliferation by targeting CDK1. Cancer Biomark 20(4):539–546

    Article  CAS  Google Scholar 

  • Sun HJ et al (2017) Activation of endocannabinoid receptor 2 as a mechanism of propofol pretreatment-induced cardioprotection against ischemia-reperfusion injury in rats. Oxid Med Cell Longev 2017:2186383

    PubMed  PubMed Central  Google Scholar 

  • Wan FZ et al (2020) Exosomes overexpressing miR-34c inhibit malignant behavior and reverse the radioresistance of nasopharyngeal carcinoma. J Transl Med 18(1):12

    Article  CAS  Google Scholar 

  • Wang Q, Zhang W, Hao S (2017) LncRNA CCAT1 modulates the sensitivity of paclitaxel in nasopharynx cancers cells via miR-181a/CPEB2 axis. Cell Cycle 16(8):795–801

    Article  CAS  Google Scholar 

  • Wang HT et al (2019) MYCT1 represses apoptosis of laryngeal cancerous cells through the MAX/miR-181a/NPM1 pathway. FEBS J 286(19):3892–3908

    Article  CAS  Google Scholar 

  • Wang L, Zhang L, Wang L (2020a) SNHG7 contributes to the progression of non-small-cell lung cancer via the SNHG7/miR-181a-5p/E2F7 axis. Cancer Manag Res 12:3211–3222

    Article  CAS  Google Scholar 

  • Wang Q et al (2020ba) Comparison of induction chemotherapy plus concurrent chemoradiotherapy and induction chemotherapy plus radiotherapy in locally advanced nasopharyngeal carcinoma. Oral Oncol 111:104925

    Article  CAS  Google Scholar 

  • Wang J et al (2020cb) Exosome-transmitted long non-coding RNA SENP3-EIF4A1 suppresses the progression of hepatocellular carcinoma. Aging (Albany NY) 12(12):11550–11567

    Article  CAS  Google Scholar 

  • Wu SH et al (2020) Tetrandrine inhibits cell migration and invasion in human nasopharyngeal carcinoma NPC-TW 039 cells through inhibiting MAPK and RhoA signaling pathways. J Food Biochem 44:e13387

    CAS  Google Scholar 

  • Xie K et al (2019) Exosomal miR-1246 derived from human umbilical cord blood mesenchymal stem cells attenuates hepatic ischemia reperfusion injury by modulating T helper 17/regulatory T balance. IUBMB Life 71(12):2020–2030

    Article  CAS  Google Scholar 

  • Yuan L et al (2019) Exosomes derived from microRNA-148b-3p-overexpressing human umbilical cord mesenchymal stem cells restrain breast cancer progression. Front Oncol 9:1076

    Article  Google Scholar 

Download references

Acknowledgements

We would like to acknowledge the reviewers for their helpful comments on this paper.

Funding

The financial reports of The Self-funded Research Projects of National Health and Family Planning Commission of Guangxi (NO. Z20170226); Basic Ability Improvement Project for young and middle-aged Teachers in Universities of Guangxi (NO. 2018KY0451); 2018 Guangxi scholarship Fund of Guangxi Education Department; Special Funding for Guangxi Special Experts (No. GRCT[2019]13#); Guangxi Medical High-level Leading Talents Training “139” Project (No. GWKJ[2018] 22#).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Qianli Tang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

432_2021_3684_MOESM1_ESM.eps

Supplementary file1 (EPS 14520 KB) Supplementary Figure 1 hUC-MSCs-derived exosomes restrict SUNE1 cell growth in vitro. A. CCK-8 assay detected SUNE1 cell proliferation; B. Colony formation assay detected SUNE1 cell colony formation ability; C. Flow cytometry detected SUNE1 cell cycle; D. Flow cytometry detected SUNE1 cell apoptosis E. Transwell assay detected SUNE1 cell migration; F. Transwell assay detected SUNE1 cell invasion; the data in the figure were all measurement data, showing as mean ± standard deviation (n = 3). * P < 0.05 compared with the PBS group. The comparison between two groups was analyzed by independent sample t test.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, J., Zhu, M. & Tang, Q. Human umbilical cord mesenchymal stem cells-derived exosomal microRNA-181a retards nasopharyngeal carcinoma development by mediating KDM5C. J Cancer Res Clin Oncol 147, 2867–2877 (2021). https://doi.org/10.1007/s00432-021-03684-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-021-03684-6

Keywords

Navigation