Skip to main content

Advertisement

Log in

Exosomal miR-214-3p as a potential novel biomarker for rhabdoid tumor of the kidney

  • Original Article
  • Published:
Pediatric Surgery International Aims and scope Submit manuscript

Abstract

Purpose

Rhabdoid tumor of the kidney (RTK) is a rare, highly aggressive pediatric renal tumor. No specific biomarkers are available for detection of RTK, and the initial differential diagnosis from other pediatric abdominal tumors, including neuroblastoma (NB), is difficult. Exosomal miRNAs are novel cancer biomarkers that can be detected in biological fluids. We explored candidate RTK-specific exosomal miRNAs as novel biomarkers of RTK.

Methods

Exosomal miRNAs were collected from conditioned media of human RTK-derived cell lines, a human embryonic renal cell line, and human NB-derived cell lines. miRNA sequencing (miRNA-Seq) was performed to detect candidate RTK-specific exosomal miRNAs. The exosomal miRNA expression in conditioned media of tumor cell lines and serum from RTK xenograft-bearing mice was analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).

Results

The expression of exosomal miR-214-3p detected by miRNA-Seq was highest in RTK-derived cell lines. Exosomal miR-214-3p expression level determined by qRT-PCR was significantly higher in RTK-derived cell lines than in the human embryonic renal cell line or NB-derived cell lines. Furthermore, the serum exosomal miR-214-3p expression level was significantly higher in RTK xenograft mice than controls.

Conclusion

Our data indicated that exosomal miR-214-3p has potential as a novel biomarker of RTK.

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

Similar content being viewed by others

Data availability

The datasets used and/or analyzed during the present study are available from the corresponding author upon reasonable request.

References

  1. Dome JS, Fernandez CV, Mullen EA, Kalapurakal JA, Geller JI, Huff V, Gratias EJ, Dix DB, Ehrlich PF, Khanna G, Malogolowkin MH, Anderson JR, Naranjo A, Perlman EJ, Committee COGRT (2013) Children’s Oncology Group’s 2013 blueprint for research: renal tumors. Pediatr Blood Cancer 60:994–1000. https://doi.org/10.1002/pbc.24419

    Article  PubMed  Google Scholar 

  2. Pastore G, Znaor A, Spreafico F, Graf N, Pritchard-Jones K, Steliarova-Foucher E (2006) Malignant renal tumours incidence and survival in European children (1978–1997): report from the automated childhood cancer information system project. Eur J Cancer 42:2103–2114. https://doi.org/10.1016/j.ejca.2006.05.010

    Article  PubMed  Google Scholar 

  3. Whittle SB, Smith V, Doherty E, Zhao S, McCarty S, Zage PE (2017) Overview and recent advances in the treatment of neuroblastoma. Expert Rev Anticancer Ther 17:369–386. https://doi.org/10.1080/14737140.2017.1285230

    Article  CAS  PubMed  Google Scholar 

  4. van den Heuvel-Eibrink MM, van Tinteren H, Rehorst H, Coulombe A, Patte C, de Camargo B, de Kraker J, Leuschner I, Lugtenberg R, Pritchard-Jones K, Sandstedt B, Spreafico F, Graf N, Vujanic GM (2011) Malignant rhabdoid tumours of the kidney (MRTKs), registered on recent SIOP protocols from 1993 to 2005: a report of the SIOP renal tumour study group. Pediatr Blood Cancer 56:733–737. https://doi.org/10.1002/pbc.22922

    Article  PubMed  Google Scholar 

  5. Sun L, Li D, Song K, Wei J, Yao S, Li Z, Su X, Ju X, Chao L, Deng X, Kong B, Li L (2017) Exosomes derived from human umbilical cord mesenchymal stem cells protect against cisplatin-induced ovarian granulosa cell stress and apoptosis in vitro. Sci Rep 7:2552. https://doi.org/10.1038/s41598-017-02786-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Peterson MF, Otoc N, Sethi JK, Gupta A, Antes TJ (2015) Integrated systems for exosome investigation. Methods 87:31–45. https://doi.org/10.1016/j.ymeth.2015.04.015

    Article  CAS  PubMed  Google Scholar 

  7. Bhagirath D, Yang TL, Bucay N, Sekhon K, Majid S, Shahryari V, Dahiya R, Tanaka Y, Saini S (2018) microRNA-1246 is an exosomal biomarker for aggressive prostate cancer. Cancer Res 78:1833–1844. https://doi.org/10.1158/0008-5472.CAN-17-2069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Valentino A, Reclusa P, Sirera R, Giallombardo M, Camps C, Pauwels P, Crispi S, Rolfo C (2017) Exosomal microRNAs in liquid biopsies: future biomarkers for prostate cancer. Clin Transl Oncol 19:651–657. https://doi.org/10.1007/s12094-016-1599-5

    Article  CAS  PubMed  Google Scholar 

  9. Thind A, Wilson C (2016) Exosomal miRNAs as cancer biomarkers and therapeutic targets. J Extracell Vesicles 5:31292. https://doi.org/10.3402/jev.v5.31292

    Article  CAS  PubMed  Google Scholar 

  10. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O’Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 105:10513–10518. https://doi.org/10.1073/pnas.0804549105

    Article  PubMed  PubMed Central  Google Scholar 

  11. Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, van Eijndhoven MA, Hopmans ES, Lindenberg JL, de Gruijl TD, Wurdinger T, Middeldorp JM (2010) Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci USA 107:6328–6333. https://doi.org/10.1073/pnas.0914843107

    Article  PubMed  PubMed Central  Google Scholar 

  12. Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T (2010) Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem 285:17442–17452. https://doi.org/10.1074/jbc.M110.107821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Galardi A, Colletti M, Di Paolo V, Vitullo P, Antonetti L, Russo I, Di Giannatale A (2019) Exosomal MiRNAs in Pediatric Cancers. Int J Mol Sci 20. https://doi.org/10.3390/ijms20184600

  14. Morini M, Cangelosi D, Segalerba D, Marimpietri D, Raggi F, Castellano A, Fruci D, de Mora JF, Canete A, Yanez Y, Viprey V, Corrias MV, Carlini B, Pezzolo A, Schleiermacher G, Mazzocco K, Ladenstein R, Sementa AR, Conte M, Garaventa A, Burchill S, Luksch R, Bosco MC, Eva A, Varesio L (2019) Exosomal microRNAs from longitudinal liquid biopsies for the prediction of response to induction chemotherapy in high-risk neuroblastoma patients: a proof of concept siopen study. Cancers (Basel) 11. https://doi.org/10.3390/cancers11101476

  15. Liu W, Chen S, Liu B (2016) Diagnostic and prognostic values of serum exosomal microRNA-21 in children with hepatoblastoma: a Chinese population-based study. Pediatr Surg Int 32:1059–1065. https://doi.org/10.1007/s00383-016-3960-8

    Article  PubMed  Google Scholar 

  16. Kurahashi R, Kadomatsu T, Baba M, Hara C, Itoh H, Miyata K, Endo M, Morinaga J, Terada K, Araki K, Eto M, Schmidt LS, Kamba T, Linehan WM, Oike Y (2019) MicroRNA-204-5p: A novel candidate urinary biomarker of Xp11.2 translocation renal cell carcinoma. Cancer Sci 110:1897–1908. https://doi.org/10.1111/cas.14026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Huang CC, Cutcliffe C, Coffin C, Sorensen PH, Beckwith JB, Perlman EJ, Renal Tumor Committee of the Children's Oncology G (2006) Classification of malignant pediatric renal tumors by gene expression. Pediatr Blood Cancer 46:728-738. https://doi.org/10.1002/pbc.20773

  18. Shu P, Fu H, Zhao X, Wu C, Ruan X, Zeng Y, Liu W, Wang M, Hou L, Chen P, Yin B, Yuan J, Qiang B, Peng X (2017) MicroRNA-214 modulates neural progenitor cell differentiation by targeting Quaking during cerebral cortex development. Sci Rep 7:8014. https://doi.org/10.1038/s41598-017-08450-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Penna E, Orso F, Taverna D (2015) miR-214 as a key hub that controls cancer networks: small player, multiple functions. J Invest Dermatol 135:960–969. https://doi.org/10.1038/jid.2014.479

    Article  CAS  PubMed  Google Scholar 

  20. Liu J, Luo XJ, Xiong AW, Zhang ZD, Yue S, Zhu MS, Cheng SY (2010) MicroRNA-214 promotes myogenic differentiation by facilitating exit from mitosis via down-regulation of proto-oncogene N-ras. J Biol Chem 285:26599–26607. https://doi.org/10.1074/jbc.M110.115824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sugimoto T, Hosoi H, Horii Y, Ishida H, Mine H, Takahashi K, Abe T, Ohta S, Sawada T (1999) Malignant rhabdoid-tumor cell line showing neural and smooth-muscle-cell phenotypes. Int J Cancer 82:678–686. https://doi.org/10.1002/(sici)1097-0215(19990827)82:5%3c678::aid-ijc10%3e3.0.co;2-k

    Article  CAS  PubMed  Google Scholar 

  22. Tsokos M, Kouraklis G, Chandra RS, Bhagavan BS, Triche TJ (1989) Malignant rhabdoid tumor of the kidney and soft tissues. Evidence for a diverse morphological and immunocytochemical phenotype. Arch Pathol Lab Med 113:115–120

    CAS  PubMed  Google Scholar 

  23. Ota S, Crabbe DC, Tran TN, Triche TJ, Shimada H (1993) Malignant rhabdoid tumor. A study with two established cell lines. Cancer 71:2862–2872. https://doi.org/10.1002/1097-0142(19930501)71:9%3c2862::aid-cncr2820710930%3e3.0.co;2-d

    Article  CAS  PubMed  Google Scholar 

  24. Cai H, Miao M, Wang Z (2018) miR-214-3p promotes the proliferation, migration and invasion of osteosarcoma cells by targeting CADM1. Oncol Lett 16:2620–2628. https://doi.org/10.3892/ol.2018.8927

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wang J, Zhao X, Guo Z, Ma X, Song Y, Guo Y (2017) Regulation of NEAT1/miR-214-3p on the growth, migration and invasion of endometrial carcinoma cells. Arch Gynecol Obstet 295:1469–1475. https://doi.org/10.1007/s00404-017-4365-1

    Article  CAS  PubMed  Google Scholar 

  26. Xu C, He T, Li Z, Liu H, Ding B (2017) Regulation of HOXA11-AS/miR-214-3p/EZH2 axis on the growth, migration and invasion of glioma cells. Biomed Pharmacother 95:1504–1513. https://doi.org/10.1016/j.biopha.2017.08.097

    Article  CAS  PubMed  Google Scholar 

  27. Zhan M, He K, Xiao J, Liu F, Wang H, Xia Z, Duan X, Huang R, Li Y, He X, Yin H, Xiang G, Lu L (2018) LncRNA HOXA11-AS promotes hepatocellular carcinoma progression by repressing miR-214-3p. J Cell Mol Med 22:3758–3767. https://doi.org/10.1111/jcmm.13633

    Article  CAS  PubMed Central  Google Scholar 

  28. Wang X, Li H, Shi J (2019) LncRNA HOXA11-AS promotes proliferation and cisplatin resistance of oral squamous cell carcinoma by suppression of miR-214-3p expression. Biomed Res Int 2019:8645153. https://doi.org/10.1155/2019/8645153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Yang Y, Li Z, Yuan H, Ji W, Wang K, Lu T, Yu Y, Zeng Q, Li F, Xia W, Lu S (2019) Reciprocal regulatory mechanism between miR-214-3p and FGFR1 in FGFR1-amplified lung cancer. Oncogenesis 8:50. https://doi.org/10.1038/s41389-019-0151-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wang Z, Cai H, Lin L, Tang M, Cai H (2014) Upregulated expression of microRNA-214 is linked to tumor progression and adverse prognosis in pediatric osteosarcoma. Pediatr Blood Cancer 61:206–210. https://doi.org/10.1002/pbc.24763

    Article  PubMed  Google Scholar 

  31. Jin Y, Wong YS, Goh BKP, Chan CY, Cheow PC, Chow PKH, Lim TKH, Goh GBB, Krishnamoorthy TL, Kumar R, Ng TP, Chong SS, Tan HH, Chung AYF, Ooi L, Chang JPE, Tan CK, Lee CGL (2019) Circulating microRNAs as potential diagnostic and prognostic biomarkers in hepatocellular carcinoma. Sci Rep 9:10464. https://doi.org/10.1038/s41598-019-46872-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Schwarzenbach H, Milde-Langosch K, Steinbach B, Muller V, Pantel K (2012) Diagnostic potential of PTEN-targeting miR-214 in the blood of breast cancer patients. Breast Cancer Res Treat 134:933–941. https://doi.org/10.1007/s10549-012-1988-6

    Article  CAS  PubMed  Google Scholar 

  33. Wang J, Xu Y, Wang J, Ying H (2020) Circulating miR-214-3p predicts nasopharyngeal carcinoma recurrence or metastasis. Clin Chim Acta 503:54–60. https://doi.org/10.1016/j.cca.2020.01.002

    Article  CAS  PubMed  Google Scholar 

  34. Kim SM, Kang HW, Kim WT, Kim YJ, Yun SJ, Lee SC, Kim WJ (2013) Cell-Free microRNA-214 from urine as a biomarker for non-muscle-invasive bladder cancer. Korean J Urol 54:791–796. https://doi.org/10.4111/kju.2013.54.11.791

    Article  PubMed  PubMed Central  Google Scholar 

  35. Srivastava A, Goldberger H, Dimtchev A, Ramalinga M, Chijioke J, Marian C, Oermann EK, Uhm S, Kim JS, Chen LN, Li X, Berry DL, Kallakury BV, Chauhan SC, Collins SP, Suy S, Kumar D (2013) MicroRNA profiling in prostate cancer–the diagnostic potential of urinary miR-205 and miR-214. PLoS ONE 8:e76994. https://doi.org/10.1371/journal.pone.0076994

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Allen-Rhoades W, Kurenbekova L, Satterfield L, Parikh N, Fuja D, Shuck RL, Rainusso N, Trucco M, Barkauskas DA, Jo E, Ahern C, Hilsenbeck S, Donehower LA, Yustein JT (2015) Cross-species identification of a plasma microRNA signature for detection, therapeutic monitoring, and prognosis in osteosarcoma. Cancer Med 4:977–988. https://doi.org/10.1002/cam4.438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Ms. A. Oguni for her excellent technical support and Ms. E. Mizutani for her secretarial assistance. The present study was supported in part by JSPS KAKENHI Grant Number 17K11524 to SU.

Funding

The present study was supported in part by JSPS KAKENHI Grant Number 17K11524 to SU.

Author information

Authors and Affiliations

Authors

Contributions

Shuichiro Uehara (SU) and Eri Nagasaki-Maeoka (ENM) planned the experiments. Bin Yamaoka (BY), ENM, Shota Uekusa, Ayano Hidaka, Kohei Hijikata, and Reona Kato performed the experiments. BY, ENM, Kyoko Fujiwara (KF), and SU interpreted experimental data. BY and ENM wrote the paper. SU, Tsugumichi Koshinaga, and KF revised the manuscript critically for important intellectual content. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Shuichiro Uehara.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yamaoka, B., Nagasaki-Maeoka, E., Uekusa, S. et al. Exosomal miR-214-3p as a potential novel biomarker for rhabdoid tumor of the kidney. Pediatr Surg Int 37, 1783–1790 (2021). https://doi.org/10.1007/s00383-021-04989-w

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00383-021-04989-w

Keywords

Navigation