Skip to main content
SpringerLink
Log in

MiR-501-3p promotes osteosarcoma cell proliferation, migration and invasion by targeting BCL7A

  • Research Article
  • Published:
Human Cell Aims and scope Submit manuscript

Abstract

Increasing numbers of evidences have demonstrated that microRNAs (miRNAs) play an important role in osteosarcoma (OS) cell functions. MiR-501-3p has been reported to play an important role in several types of tumors, including prostate cancer and hepatocellular carcinoma. However, the biological function and potential mechanism of miR-501-3p in OS have not been well investigated until now. Here, we analyzed the expression of miR-501-3p in OS tissues and cell lines and its clinical significance in OS patients. Quantitative reverse transcription PCR showed miR-501-3p was significantly up-regulated in OS tissues and cell lines. Up-regulated miR-501-3p expression was associated with TNM stage, distal metastasis and worse prognosis in OS patients. MiR-501-3p knockdown and overexpression were achieved by miR-501-3p inhibitor and mimics transfection, respectively. CCK-8, colony formation and transwell assays showed that miR-501-3p knockdown in U2OS and Saos-2 cells suppressed, while miR-501-3p overexpression in Saos-2 cells promoted cell proliferation, migration and invasion. Moreover, luciferase reporter assay supporting BCL7A was a target of miR-501-3p and its expression was increased by miR-501-3p inhibitor, but inhibited by miR-501-3p mimics. By performing rescue experiments, we further demonstrated that BCL7A was a downstream functional regulator involved in miR-501-3p promoting OS cell functions. In summary, our findings suggest that miR-501-3p targets BCL7A may provide novel therapeutic targets for the treatment of OS.

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
Fig. 6

Similar content being viewed by others

Abbreviations

OS:

Osteosarcoma

3′-UTR:

3′-Untranslated region

cDNA:

Complementary DNA

DMEM:

Dulbecco’s Modified Eagle’s Medium

FBS:

Fetal bovine serum

NC:

Negative control

CCK-8:

Cell Counting Kit-8

PVDF:

Polyvinylidene fluoride

TBST:

Tris-buffered saline with Tween-20

References

  1. Mirabello L, Troisi RJ, Savage SA. International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons. Int J Cancer. 2009;125:229–34.

    Article  CAS  Google Scholar 

  2. Poletajew S, Fus L, Wasiutynski A. Current concepts on pathogenesis and biology of metastatic osteosarcoma tumors. Ortop Traumatol Rehab. 2011;13:537–45.

    Article  Google Scholar 

  3. Gorlick R. Current concepts on the molecular biology of osteosarcoma. Cancer Treat Res. 2009;152:467–78.

    Article  Google Scholar 

  4. He X, Gao Z, Xu H, Zhang Z, Fu P. A meta-analysis of randomized control trials of surgical methods with osteosarcoma outcomes. J Orthop Surg Res. 2017;12:5.

    Article  Google Scholar 

  5. Anninga JK, Gelderblom H, Fiocco M, et al. Chemotherapeutic adjuvant treatment for osteosarcoma: where do we stand? Eur J Cancer. 2011;47:2431–45.

    Article  CAS  Google Scholar 

  6. Taran SJ, Taran R, Malipatil NB. Pediatric osteosarcoma: an updated review. Indian J Med Paediatr Oncol. 2017;38:33–43.

    Article  Google Scholar 

  7. Shukla GC, Singh J, Barik S. MicroRNAs: processing, maturation, target recognition and regulatory functions. Mol Cell Pharmacol. 2011;3:83–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.

    Article  CAS  Google Scholar 

  9. Reddy KB. MicroRNA (miRNA) in cancer. Cancer Cell Int. 2015;15:38.

    Article  Google Scholar 

  10. Kasinski AL, Slack FJ. Epigenetics and genetics. MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy. Nat Rev Cancer. 2011;11:849–64.

    Article  CAS  Google Scholar 

  11. Zhang Z, Shao L, Wang Y, Luo X. MicroRNA-501-3p restricts prostate cancer growth through regulating cell cycle-related and expression-elevated protein in tumor/cyclin D1 signaling. Biochem Biophys Res Commun. 2019;509:746–52.

    Article  CAS  Google Scholar 

  12. Luo C, Yin D, Zhan H, et al. microRNA-501-3p suppresses metastasis and progression of hepatocellular carcinoma through targeting LIN7A. Cell Death Dis. 2018;9:535.

    Article  Google Scholar 

  13. Lu J, Zhou L, Wu B, et al. MiR-501-3p functions as a tumor suppressor in non-small cell lung cancer by downregulating RAP1A. Exp Cell Res. 2020;387:111752.

    Article  CAS  Google Scholar 

  14. Yin Z, Ma T, Huang B, et al. Macrophage-derived exosomal microRNA-501-3p promotes progression of pancreatic ductal adenocarcinoma through the TGFBR3-mediated TGF-beta signaling pathway. J Exp Clin Cancer Res. 2019;38:310.

    Article  Google Scholar 

  15. Huang C, Wang Q, Ma S, Sun Y, Vadamootoo AS, Jin C. A four serum-miRNA panel serves as a potential diagnostic biomarker of osteosarcoma. Int J Clin Oncol. 2019;24:976–82.

    Article  CAS  Google Scholar 

  16. Jadayel DM, Osborne LR, Coignet LJ, et al. The BCL7 gene family: deletion of BCL7B in Williams syndrome. Gene. 1998;224:35–44.

    Article  CAS  Google Scholar 

  17. Zani VJ, Asou N, Jadayel D, et al. Molecular cloning of complex chromosomal translocation t(8;14;12)(q24.1;q32.3;q24.1) in a Burkitt lymphoma cell line defines a new gene (BCL7A) with homology to caldesmon. Blood. 1996;87:3124–34.

    Article  CAS  Google Scholar 

  18. Carbone A, Bernardini L, Valenzano F, et al. Array-based comparative genomic hybridization in early-stage mycosis fungoides: recurrent deletion of tumor suppressor genes BCL7A, SMAC/DIABLO, and RHOF. Genes Chromosom Cancer. 2008;47:1067–75.

    Article  CAS  Google Scholar 

  19. van Doorn R, Zoutman WH, Dijkman R, et al. Epigenetic profiling of cutaneous T-cell lymphoma: promoter hypermethylation of multiple tumor suppressor genes including BCL7a, PTPRG, and p73. J Clin Oncol. 2005;23:3886–96.

    Article  Google Scholar 

  20. Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000;403:503–11.

    Article  CAS  Google Scholar 

  21. Martinez-Delgado B, Melendez B, Cuadros M, et al. Expression profiling of T-cell lymphomas differentiates peripheral and lymphoblastic lymphomas and defines survival related genes. Clin Cancer Res. 2004;10:4971–82.

    Article  CAS  Google Scholar 

  22. Potter N, Karakoula A, Phipps KP, et al. Genomic deletions correlate with underexpression of novel candidate genes at six loci in pediatric pilocytic astrocytoma. Neoplasia. 2008;10:757–72.

    Article  CAS  Google Scholar 

  23. Yu N, Shin S, Choi JR, Kim Y, Lee KA. Concomitant AID expression and bcl7a loss associates with accelerated phase progression and imatinib resistance in chronic myeloid leukemia. Ann Lab Med. 2017;37:177–9.

    Article  Google Scholar 

  24. Sun Z, Sun L, He M, Pang Y, Yang Z, Wang J. Low BCL7A expression predicts poor prognosis in ovarian cancer. J Ovarian Res. 2019;12:41.

    Article  Google Scholar 

  25. Jiang X, Wang W, Yang Y, et al. Identification of circulating microRNA signatures as potential noninvasive biomarkers for prediction and prognosis of lymph node metastasis in gastric cancer. Oncotarget. 2017;8:65132–42.

    Article  Google Scholar 

  26. Giunti L, Da Ros M, De Gregorio V, et al. A microRNA profile of pediatric glioblastoma: The role of NUCKS1 upregulation. Mol Clin Oncol. 2019;10:331–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Larsen AC. Conjunctival malignant melanoma in Denmark: epidemiology, treatment and prognosis with special emphasis on tumorigenesis and genetic profile. Acta Ophthalmol. 2016;94(1):1–27.

    Article  CAS  Google Scholar 

  28. Litvinov IV, Zhou Y, Kupper TS, Sasseville D. Loss of BCL7A expression correlates with poor disease prognosis in patients with early-stage cutaneous T-cell lymphoma. Leuk Lymphoma. 2013;54:653–4.

    Article  CAS  Google Scholar 

Download references

Funding

Not applicable.

Author information

Authors and Affiliations

  1. Department of Joint Sports Medicine, Tengzhou Central People’s Hospital, No.181 Xingtan Road, Tengzhou, 277599, Shandong, China

    Jinliang Dai, Lixin Kang & Jian Zhang

  2. Department of Neurosurgical Intensive Care Unit, Tengzhou Central People’s Hospital, Tengzhou, 277599, Shandong, China

    Lin Lu

Authors
  1. Jinliang Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lin Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lixin Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jian Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jian Zhang.

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.

Supplementary file1 (XLSX 16 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dai, J., Lu, L., Kang, L. et al. MiR-501-3p promotes osteosarcoma cell proliferation, migration and invasion by targeting BCL7A. Human Cell 34, 624–633 (2021). https://doi.org/10.1007/s13577-020-00468-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-020-00468-x

Keywords

Search

Navigation