Skip to main content

Advertisement

SpringerLink
Log in

The combined restoration of miR-424-5p and miR-142-3p effectively inhibits MCF-7 breast cancer cell line via modulating apoptosis, proliferation, colony formation, cell cycle and autophagy

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Background

The combined restoration of tumor-suppressive microRNAs (miRs) has been identified as a promising approach for inhibiting breast cancer development. This study investigated the effect of the combined restoration of miR-424-5p and miR-142-3p on MCF-7 cells and compared the efficacy of the combined therapy with the monotherapies with miR-424-5p and miR-142-3p.

Methods

After transfection of miR-424-5p and miR-142-3p mimics into MCF-7 cells in the combined and separated manner, the proliferation of tumoral cells was assessed by the MTT assay. Also, the apoptosis, autophagy, and cell cycle of the cells were analyzed by flow cytometry. Western blot and qRT-PCR were used to study the expression levels of c-Myc, Bcl-2, Bax, STAT-3, Oct-3, and Beclin-1.

Results

Our results have demonstrated that the combined restoration of miR-424-5p and miR-142-3p is more effective in inhibiting tumor proliferation via upregulating Bax and Beclin-1 and downregulating Bcl-2 and c-Myc. Besides, the combined therapy has arrested the cell cycle in the sub-G1 and G2 phases and has suppressed the clonogenicity via downregulating STAT-3 and Oct-3, respectively.

Conclusion

The combined restoration of miR-424-5p and miR-142-3p is more effective in inhibiting MCF-7 breast cancer development than monotherapies with miR-424-5p and miR-142-3p.

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

The data would be available if requested by Editor or reviewers. They would be provided by Dr. Safaralizadeh (corresponding author).

References

  1. Momenimovahed Z, Salehiniya H (2019) Epidemiological characteristics of and risk factors for breast cancer in the world. Breast Cancer (Dove Med Press) 11:151–164

    Google Scholar 

  2. Yao H, He G, Yan S et al (2017) Triple-negative breast cancer: is there a treatment on the horizon? Oncotarget 8:1913–1924

    Article  PubMed  Google Scholar 

  3. Maeda H, Khatami M (2018) Analyses of repeated failures in cancer therapy for solid tumors: poor tumor-selective drug delivery, low therapeutic efficacy and unsustainable costs. Clin Transl Med 7:11

    Article  PubMed  PubMed Central  Google Scholar 

  4. Ahangar NK, Hemmat N, Khalaj-Kondori M et al (2021) The regulatory cross-talk between microRNAs and novel members of the B7 family in human diseases: a scoping review. Int J Mol Sci 22(5):2652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lin YC, Chen TH, Huang YM, Wei PL, Lin JC (2021) Involvement of microRNA in solid cancer: role and regulatory mechanisms. Biomedicines 9(4):343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bertoli G, Cava C, Castiglioni I (2015) MicroRNAs: new biomarkers for diagnosis, prognosis, therapy prediction and therapeutic tools for breast cancer. Theranostics 5:1122–1143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Dastmalchi N, Safaralizadeh R, SM BK, et al (2021) An updated review of the cross-talk between micrornas and epigenetic factors in cancers. Curr Med Chem 28(42):8722–8732

    Article  PubMed  Google Scholar 

  8. Mansoori B, Mohammadi A, Ghasabi M et al (2019) miR-142-3p as tumor suppressor miRNA in the regulation of tumorigenicity, invasion and migration of human breast cancer by targeting Bach-1 expression. J Cell Physiol 234:9816–9825

    Article  CAS  PubMed  Google Scholar 

  9. Dastmalchi N, Safaralizadeh R, Baradaran B, Hosseinpourfeizi M, Baghbanzadeh A (2020) An update review of deregulated tumor suppressive microRNAs and their contribution in various molecular subtypes of breast cancer. Gene 729:144301

    Article  CAS  PubMed  Google Scholar 

  10. Mollaei H, Safaralizadeh R, Rostami Z (2019) MicroRNA replacement therapy in cancer. J Cell Physiol 234:12369–12384

    Article  CAS  PubMed  Google Scholar 

  11. Dastmalchi N, Hosseinpourfeizi MA, Khojasteh SMB, Baradaran B, Safaralizadeh R (2020) Tumor suppressive activity of miR-424-5p in breast cancer cells through targeting PD-L1 and modulating PTEN/PI3K/AKT/mTOR signaling pathway. Life Sci 259:118239

    Article  CAS  PubMed  Google Scholar 

  12. Mansoori B, Duijf PH, Mohammadi A et al (2021) MiR-142-3p targets HMGA2 and suppresses breast cancer malignancy. Life Sci 276:119431

    Article  CAS  PubMed  Google Scholar 

  13. Zhou Y, Yamamoto Y, Takeshita F, Yamamoto T, Xiao Z, Ochiya T (2021) Delivery of miR-424-5p via extracellular vesicles promotes the apoptosis of MDA-MB-231 TNBC cells in the tumor microenvironment. Int J Mol Sci 22:844

    Article  CAS  PubMed Central  Google Scholar 

  14. Xie D, Song H, Wu T et al (2018) MicroRNA-424 serves an anti-oncogenic role by targeting cyclin-dependent kinase 1 in breast cancer cells. Oncol Rep 40:3416–3426

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Wang J, Wang S, Zhou J, Qian Q (2018) miR-424-5p regulates cell proliferation, migration and invasion by targeting doublecortin-like kinase 1 in basal-like breast cancer. Biomed Pharmacother 102:147–152

    Article  CAS  PubMed  Google Scholar 

  16. Liang L, Fu J, Wang S et al (2020) MiR-142-3p enhances chemosensitivity of breast cancer cells and inhibits autophagy by targeting HMGB1. Acta Pharm Sin B 10:1036–1046

    Article  CAS  PubMed  Google Scholar 

  17. Mansoori B, Mohammadi A, Gjerstorff MF et al (2019) miR-142-3p is a tumor suppressor that inhibits estrogen receptor expression in ER-positive breast cancer. J Cell Physiol 234:16043–16053

    Article  CAS  Google Scholar 

  18. Zhou Y, Yamamoto Y, Takeshita F, Yamamoto T, Xiao Z, Ochiya T (2021) Delivery of miR-424–5p via extracellular vesicles promotes the apoptosis of MDA-MB-231 TNBC cells in the tumor microenvironment. Int J Mol Sci 22(2):844

    Article  CAS  PubMed Central  Google Scholar 

  19. Zhao Y, Zhu C, Chang Q et al (2020) MiR-424-5p regulates cell cycle and inhibits proliferation of hepatocellular carcinoma cells by targeting E2F7. PLoS ONE 15:e0242179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Derakhshani A, Rostami Z, Safarpour H et al (2021) From oncogenic signaling pathways to single-cell sequencing of immune cells: changing the landscape of cancer immunotherapy. Molecules 26:2278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Potter H (2003) Transfection by electroporation. Curr Protoc Mol Biol 9(9):3

    PubMed  Google Scholar 

  22. Rodriguez-Barrueco R, Nekritz EA, Bertucci F et al (2017) miR-424(322)/503 is a breast cancer tumor suppressor whose loss promotes resistance to chemotherapy. Genes Dev 31:553–566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Tolosa L, Donato MT, Gomez-Lechon MJ (2015) General cytotoxicity assessment by means of the MTT assay. Methods Mol Biol 1250:333–348

    Article  CAS  PubMed  Google Scholar 

  24. Huang L, Jiang Y, Chen Y (2017) Predicting drug combination index and simulating the network-regulation dynamics by mathematical modeling of drug-targeted EGFR-ERK signaling pathway. Sci Rep 7:40752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Mansoori B, Mohammadi A, Gjerstorff MF et al (2019) miR-142–3p is a tumor suppressor that inhibits estrogen receptor expression in ER-positive breast cancer. J Cell Physiol 4(9):16043–16053

    Article  Google Scholar 

  26. Redig AJ, McAllister SS (2013) Breast cancer as a systemic disease: a view of metastasis. J Intern Med 274:113–126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Mansoori B, Silvestris N, Mohammadi A et al (2021) miR-34a and miR-200c have an additive tumor-suppressive effect on breast cancer cells and patient prognosis. Genes 12:267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Mansoori B, Silvestris N, Mohammadi A et al (2021) miR-34a and miR-200c have an additive tumor-suppressive effect on breast cancer cells and patient prognosis. Genes (Basel) 12(2):267

    Article  CAS  Google Scholar 

  29. Zhang T, Ji C, Shi R (2019) miR-142-3p promotes pancreatic beta cell survival through targeting FOXO1 in gestational diabetes mellitus. Int J Clin Exp Pathol 12:1529–1538

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Kastingschafer CS, Schafer SD, Kiesel L, Gotte M (2015) miR-142-3p is a novel regulator of cell viability and proinflammatory signalling in endometrial stroma cells. Reprod Biomed Online 30:553–556

    Article  PubMed  Google Scholar 

  31. Xie D, Song H, Wu T et al (2018) MicroRNA424 serves an antioncogenic role by targeting cyclindependent kinase 1 in breast cancer cells. Oncol Rep 40:3416–3426

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Dastmalchi N, Baradaran B, Banan Khojasteh SM, Hosseinpourfeizi M, Safaralizadeh R (2020) miR-424: a novel potential therapeutic target and prognostic factor in malignancies. Cell Biol Int 45(4):720–730

    Article  PubMed  Google Scholar 

  33. Dastmalchi N, Safaralizadeh R, Hosseinpourfeizi MA, Baradaran B, Khojasteh SMB (2021) MicroRNA-424-5p enhances chemosensitivity of breast cancer cells to Taxol and regulates cell cycle, apoptosis, and proliferation. Mol Biol Rep 48:1345–1357

    Article  CAS  PubMed  Google Scholar 

  34. Valovka T, Schonfeld M, Raffeiner P et al (2013) Transcriptional control of DNA replication licensing by Myc. Sci Rep 3:3444

    Article  PubMed  PubMed Central  Google Scholar 

  35. Shadbad MA, Hajiasgharzadeh K, Baradaran B (2020) Cross-talk between myeloid-derived suppressor cells and Mucin1 in breast cancer vaccination: on the verge of a breakthrough. Life Sci 258:118128

    Article  Google Scholar 

  36. Zaytseva YY, Rychahou PG, Gulhati P et al (2012) Inhibition of fatty acid synthase attenuates CD44-associated signaling and reduces metastasis in colorectal cancer. Cancer Res 72:1504–1517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ma L, Li Z, Li W, Ai J, Chen X (2019) MicroRNA-142-3p suppresses endometriosis by regulating KLF9-mediated autophagy in vitro and in vivo. RNA Biol 16:1733–1748

    Article  PubMed  PubMed Central  Google Scholar 

  38. Lu HT, Xu YQ, Wang H, Zhang XL (2020) miR-424-5p regulates apoptosis and cell proliferation via targeting Bcl2 in nucleus pulposus cells. Anim Cells Syst (Seoul) 24:136–142

    Article  CAS  Google Scholar 

  39. Zhao FQ, Misra Y, Li DB et al (2018) Differential expression of Oct3/4 in human breast cancer and normal tissues. Int J Oncol 52:2069–2078

    CAS  PubMed  Google Scholar 

  40. Karmakar S, Seshacharyulu P, Lakshmanan I et al (2017) hPaf1/PD2 interacts with OCT3/4 to promote self-renewal of ovarian cancer stem cells. Oncotarget 8:14806

    Article  PubMed  PubMed Central  Google Scholar 

  41. Shen WW, Zeng Z, Zhu WX, Fu GH (2013) MiR-142-3p functions as a tumor suppressor by targeting CD133, ABCG2, and Lgr5 in colon cancer cells. J Mol Med (Berl) 91:989–1000

    Article  CAS  Google Scholar 

  42. Marquez RT, Xu L (2012) Bcl-2: Beclin 1 complex: multiple, mechanisms regulating autophagy/apoptosis toggle switch. Am J Cancer Res 2:214–221

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Gozuacik D, Akkoc Y, Ozturk DG, Kocak M (2017) Autophagy-regulating microRNAs and cancer. Front Oncol 7:65

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We appreciated Immunology research center of Tabriz (IRC) for providing facilities.

Funding

The authors have not disclosed any funding.

Author information

Authors and Affiliations

  1. Department of Biology, University College of Nabi Akram, Tabriz, Iran

    Narges Dastmalchi

  2. Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran

    Reza Safaralizadeh, Seyed Mahdi Banan Khojasteh, Mohammad Ali Hosseinpourfeizi, Shirin Azarbarzin & Ali Rajabi

  3. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran

    Mahdi Abdoli Shadbad

  4. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Behzad Baradaran

Authors
  1. Narges Dastmalchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Reza Safaralizadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seyed Mahdi Banan Khojasteh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mahdi Abdoli Shadbad
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohammad Ali Hosseinpourfeizi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shirin Azarbarzin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ali Rajabi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Behzad Baradaran
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

ND acquired and analyzed the data and wrote the manuscript, RS designed the work, SMB and MH wrote and revised the manuscript, MA substantially revised the manuscript, BB, ShA, and AR drafted the work and revised the manuscript.

Corresponding author

Correspondence to Reza Safaralizadeh.

Ethics declarations

Conflict of interest

The authors have not disclosed any competing interests.

Ethical approval

Not applicable. This project has not used any human or animal samples.

Consent for publication

Not applicable.

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 (DOCX 16 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dastmalchi, N., Safaralizadeh, R., Khojasteh, S.M.B. et al. The combined restoration of miR-424-5p and miR-142-3p effectively inhibits MCF-7 breast cancer cell line via modulating apoptosis, proliferation, colony formation, cell cycle and autophagy. Mol Biol Rep 49, 8325–8335 (2022). https://doi.org/10.1007/s11033-022-07646-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-022-07646-0

Keywords

Search

Navigation