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Homo sapiens circular RNA 0003602 (Hsa_circ_0003602) accelerates the tumorigenicity of acute myeloid leukemia by modulating miR-502-5p/IGF1R axis

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Abstract

Acute myeloid leukemia (AML) has become a worldwide malignant cancer. We intended to investigate the critical roles and mechanism underlying homo sapiens circular RNA 0003602 (hsa_circ_0003602) in AML progression, especially in tumor cell proliferation, migration, invasion, and apoptosis. Real-time PCR was applied to identify the differential expression of hsa_circ_0003602 and miR-502-5p in AML bone marrow tissues and cell lines. In addition, western blot analysis was employed to determine the levels insulin-like growth factor 1 receptor (IGF1R) protein. The biological behaviors were assessed by CCK-8 cell viability assay, flow cytometry assay for apoptosis detection, and Transwell migration and invasion assay. The relationships between target miRNA and downstream mRNA were investigated by bioinformatics, luciferase reporter assay, and biotin-labeled RNA pull-down assay. Hsa_circ_0003602 was upregulated and predicted poor survival in AML. Knockdown of hsa_circ_0003602 in AML cell lines induced the inhibition of proliferation, migration, and invasion and caused apoptosis. Hsa_circ_0003602 sequestered miR-502-5p by functioning as a competitive endogenous RNA (ceRNA), thereby regulating IGF1R expression. Hsa_circ_0003602 acted as a tumor promoter in AML via miR-502-5p/IGF1R axis. Our study provides evidence that hsa_circ_0003602, miR-502-5p, and IGF1R might form a regulatory axis to affect the carcinogenicity of AML cells and provide potential targets for the treatment of AML.

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Data availability

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

Abbreviations

AML:

Acute myeloid leukemia

ceRNA:

Competitive endogenous RNA

IGF1R:

Insulin-like growth factor 1 receptor

CircRNA:

Circular RNA

CRC:

Colorectal cancer

References

  1. Vakiti A, Mewawalla P (2020) Acute myeloid leukemia. StatPearls, Treasure Island

    Google Scholar 

  2. Loke J, Malladi R, Moss P, Craddock C (2020) The role of allogeneic stem cell transplantation in the management of acute myeloid leukaemia: a triumph of hope and experience. Br J Haematol 188:129–146. https://doi.org/10.1111/bjh.16355

    Article  PubMed  Google Scholar 

  3. DiNardo CD, Maiti A, Rausch CR, Pemmaraju N, Naqvi K, Daver NG, Kadia TM, Borthakur G, Ohanian M, Alvarado Y, Issa GC, Montalban-Bravo G, Short NJ, Yilmaz M, Bose P, Jabbour EJ, Takahashi K, Burger JA, Garcia-Manero G, Jain N, Kornblau SM, Thompson PA, Estrov Z, Masarova L, Sasaki K, Verstovsek S, Ferrajoli A, Weirda WG, Wang SA, Konoplev S, Chen Z, Pierce SA, Ning J, Qiao W, Ravandi F, Andreeff M, Welch JS, Kantarjian HM, Konopleva MY (2020) 10-day decitabine with venetoclax for newly diagnosed intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: a single-centre, phase 2 trial. Lancet Haematol 7:e724–e736. https://doi.org/10.1016/S2352-3026(20)30210-6

    Article  PubMed  PubMed Central  Google Scholar 

  4. Cui L, Liu Y, Pang Y, Qian T, Quan L, Cheng Z, Dai Y, Ye X, Pang Y, Shi J, Ke X, Wu D, Fu L (2020) Emerging agents and regimens for treatment of relapsed and refractory acute myeloid leukemia. Cancer Gene Ther 27:1–14. https://doi.org/10.1038/s41417-019-0119-5

    Article  CAS  PubMed  Google Scholar 

  5. Schwarzer A, Emmrich S, Schmidt F, Beck D, Ng M, Reimer C, Adams FF, Grasedieck S, Witte D, Kabler S, Wong JWH, Shah A, Huang Y, Jammal R, Maroz A, Jongen-Lavrencic M, Schambach A, Kuchenbauer F, Pimanda JE, Reinhardt D, Heckl D, Klusmann JH (2017) The non-coding RNA landscape of human hematopoiesis and leukemia. Nat Commun 8:218. https://doi.org/10.1038/s41467-017-00212-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Jamal M, Song T, Chen B, Faisal M, Hong Z, Xie T, Wu Y, Pan S, Yin Q, Shao L, Zhang Q (2019) recent Progress on circular RNA research in acute myeloid leukemia. Front Oncol 9:1108. https://doi.org/10.3389/fonc.2019.01108

    Article  PubMed  PubMed Central  Google Scholar 

  7. Liu J, Li D, Luo H, Zhu X (2019) Circular RNAs: the star molecules in cancer. Mol Aspects Med 70:141–152. https://doi.org/10.1016/j.mam.2019.10.006

    Article  CAS  PubMed  Google Scholar 

  8. Kristensen LS, Andersen MS, Stagsted LVW, Ebbesen KK, Hansen TB, Kjems J (2019) The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet 20:675–691. https://doi.org/10.1038/s41576-019-0158-7

    Article  CAS  PubMed  Google Scholar 

  9. Ji T, Chen Q, Tao S, Shi Y, Chen Y, Shen L, Wang C, Yu L (2019) The research progress of circular RNAs in hematological malignancies. Hematology 24:727–731. https://doi.org/10.1080/16078454.2019.1669924

    Article  CAS  PubMed  Google Scholar 

  10. Perez de Acha O, Rossi M, Gorospe M (2020) Circular RNAs in blood malignancies. Front Mol Biosci 7:109. https://doi.org/10.3389/fmolb.2020.00109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chen MS, Lin CH, Huang LY, Qiu XM (2020) CircRNA SMARCC1 sponges MiR-140-3p to regulate cell progression in colorectal cancer. Cancer Manag Res 12:4899–4910. https://doi.org/10.2147/CMAR.S254185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cheng Y, Su Y, Wang S, Liu Y, Jin L, Wan Q, Liu Y, Li C, Sang X, Yang L, Liu C, Wang Z (2020) Identification of circRNA-lncRNA-miRNA-mRNA competitive endogenous RNA network as novel prognostic markers for acute myeloid leukemia. Genes (Basel). https://doi.org/10.3390/genes11080868

    Article  PubMed Central  Google Scholar 

  13. Karmali R, Larson ML, Shammo JM, Basu S, Christopherson K, Borgia JA, Venugopal P (2015) Impact of insulin-like growth factor 1 and insulin-like growth factor binding proteins on outcomes in acute myeloid leukemia. Leuk Lymphoma 56:3135–3142. https://doi.org/10.3109/10428194.2015.1022767

    Article  CAS  PubMed  Google Scholar 

  14. Xu DD, Wang Y, Zhou PJ, Qin SR, Zhang R, Zhang Y, Xue X, Wang J, Wang X, Chen HC, Wang X, Pan YW, Zhang L, Yan HZ, Liu QY, Liu Z, Chen SH, Chen HY, Wang YF (2018) The IGF2/IGF1R/Nanog signaling pathway regulates the proliferation of acute myeloid leukemia stem cells. Front Pharmacol 9:687. https://doi.org/10.3389/fphar.2018.00687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Chen L, Jiang X, Chen H, Han Q, Liu C, Sun M (2019) microRNA-628 inhibits the proliferation of acute myeloid leukemia cells by directly targeting IGF-1R. Onco Targets Ther 12:907–919. https://doi.org/10.2147/OTT.S192137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Fan H, Li Y, Liu C, Liu Y, Bai J, Li W (2018) Circular RNA-100290 promotes cell proliferation and inhibits apoptosis in acute myeloid leukemia cells via sponging miR-203. Biochem Biophys Res Commun 507:178–184. https://doi.org/10.1016/j.bbrc.2018.11.002

    Article  CAS  PubMed  Google Scholar 

  17. Zhou J, Zhou LY, Tang X, Zhang J, Zhai LL, Yi YY, Yi J, Lin J, Qian J, Deng ZQ (2019) Circ-Foxo3 is positively associated with the Foxo3 gene and leads to better prognosis of acute myeloid leukemia patients. BMC Cancer 19:930. https://doi.org/10.1186/s12885-019-5967-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Yi YY, Yi J, Zhu X, Zhang J, Zhou J, Tang X, Lin J, Wang P, Deng ZQ (2019) Circular RNA of vimentin expression as a valuable predictor for acute myeloid leukemia development and prognosis. J Cell Physiol 234:3711–3719. https://doi.org/10.1002/jcp.27145

    Article  CAS  PubMed  Google Scholar 

  19. Yi L, Zhou L, Luo J, Yang Q (2020) Circ-PTK2 promotes the proliferation and suppressed the apoptosis of acute myeloid leukemia cells through targeting miR-330-5p/FOXM1 axis. Blood Cells Mol Dis 86:102506. https://doi.org/10.1016/j.bcmd.2020.102506

    Article  CAS  PubMed  Google Scholar 

  20. Wang Y, Guo T, Liu Q, Xie X (2020) CircRAD18 accelerates the progression of acute myeloid leukemia by modulation of miR-206/PRKACB Axis. Cancer Manag Res 12:10887–10896. https://doi.org/10.2147/CMAR.S277432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Guo J, Duan H, Li Y, Yang L, Yuan L (2019) A novel circular RNA circ-ZNF652 promotes hepatocellular carcinoma metastasis through inducing snail-mediated epithelial-mesenchymal transition by sponging miR-203/miR-502-5p. Biochem Biophys Res Commun 513:812–819. https://doi.org/10.1016/j.bbrc.2019.03.214

    Article  CAS  PubMed  Google Scholar 

  22. Wei Y, Lu C, Zhou P, Zhao L, Lyu X, Yin J, Shi Z, You YP (2020) EIF4A3-induced circular RNA ASAP1(circASAP1) promotes tumorigenesis and temozolomide resistance of glioblastoma via NRAS/MEK1/ERK1/2 signaling. Neuro Oncol. https://doi.org/10.1093/neuonc/noaa214

    Article  PubMed  PubMed Central  Google Scholar 

  23. Ying Y, Li J, Xie H, Yan H, Jin K, He L, Ma X, Wu J, Xu X, Fang J, Wang X, Zheng X, Liu B, Xie L (2020) CCND1, NOP14 and DNMT3B are involved in miR-502-5p-mediated inhibition of cell migration and proliferation in bladder cancer. Cell Prolif 53:e12751. https://doi.org/10.1111/cpr.12751

    Article  PubMed  PubMed Central  Google Scholar 

  24. Hakuno F, Takahashi SI (2018) IGF1 receptor signaling pathways. J Mol Endocrinol 61:T69–T86. https://doi.org/10.1530/JME-17-0311

    Article  CAS  PubMed  Google Scholar 

  25. Qi J, Shi LY, Wu Y, Shen XJ, Yuan J, Jin CJ, Cong H, Ju SQ (2019) Epigenetic silencing of miR-335 induces migration by targeting insulin-like growth factor-1 receptor in multiple myeloma. Leuk Lymphoma 60:3188–3198. https://doi.org/10.1080/10428194.2019.1627534

    Article  CAS  PubMed  Google Scholar 

  26. Du P, Liu F, Liu Y, Shao M, Li X, Qin G (2020) Linc00210 enhances the malignancy of thyroid cancer cells by modulating miR-195-5p/IGF1R/Akt axis. J Cell Physiol 235:1001–1012. https://doi.org/10.1002/jcp.29016

    Article  CAS  PubMed  Google Scholar 

  27. Somri-Gannam L, Meisel-Sharon S, Hantisteanu S, Groisman G, Limonad O, Hallak M, Bruchim I (2020) IGF1R axis inhibition restores dendritic cell antitumor response in ovarian cancer. Transl Oncol 13:100790. https://doi.org/10.1016/j.tranon.2020.100790

    Article  PubMed  PubMed Central  Google Scholar 

  28. Zhang M, Lin B, Liu Y, Huang T, Chen M, Lian D, Deng S, Zhuang C (2020) LINC00324 affects non-small cell lung cancer cell proliferation and invasion through regulation of the miR-139-5p/IGF1R axis. Mol Cell Biochem 473:193–202. https://doi.org/10.1007/s11010-020-03819-2

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by Zhejiang Medicine Health Science and Technology Plan (2020KY254).

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Authors and Affiliations

  1. Department of Pediatrics, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, No. 59 Liuting Street, Ningbo, 315000, Zhejiang Province, People’s Republic of China

    Qidong Ye, Nan Li, Kai Zhou & Cong Liao

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  1. Qidong Ye
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  2. Nan Li
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  3. Kai Zhou
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  4. Cong Liao
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Contributions

QDY and NL conceived and designed the experiments; KZ and CL analyzed and interpreted the results of the experiments; KZ and CL performed the experiments; all authors have read and approved the manuscript.

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Correspondence to Qidong Ye.

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Ye, Q., Li, N., Zhou, K. et al. Homo sapiens circular RNA 0003602 (Hsa_circ_0003602) accelerates the tumorigenicity of acute myeloid leukemia by modulating miR-502-5p/IGF1R axis. Mol Cell Biochem 477, 635–644 (2022). https://doi.org/10.1007/s11010-021-04277-0

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  • DOI: https://doi.org/10.1007/s11010-021-04277-0

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