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Effects of CD44 siRNA on inhibition, survival, and apoptosis of breast cancer cell lines (MDA-MB-231 and 4T1)

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Abstract

Background

Breast cancer (BC) is one of the most common cancers in the world. Despite the many advances that have been made in treating patients, many patients are still resistant to treatment. CD44 is one of the surface glycoproteins of BC cells that plays an important role in the proliferation of these cells and inhibition of their apoptosis. Therefore, targeting it can be a treatment way for BC patients.

Methods

In this study, the effect of anti-CD44 siRNA on the proliferation, apoptosis, and migration rate of MDA-MB-231 and 4T1 cells was investigated. The techniques used in this study were MTT assay, RT-PCR, and flow cytometry.

Results

The apoptosis and proliferation rates in CD44 siRNA-treated cells were higher and lower, respectively, compared to untreated cells. Also, cell migration was less in treated cells compared to untreated cells. CD44 siRNA also decreased the expression of CXCR4, c-myc, Vimentin, ROCK, and MMP-9.

Conclusion

Finally, CD44 targeting can be a good treatment option to make BC cells more sensitive to apoptosis.

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Availability of data and materials

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

References

  1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E86

    Article  CAS  PubMed  Google Scholar 

  2. Campbell LL, Polyak K (2007) Breast tumor heterogeneity: cancer stem cells or clonal evolution? Cell Cycle 6(19):2332–2338

    Article  CAS  PubMed  Google Scholar 

  3. Kaboli PJ, Shabani S, Sharma S, Nasr MP, Yamaguchi H, Hung MC (2022) Shedding light on triple-negative breast cancer with Trop2-targeted antibody-drug conjugates. Am J cancer Res 12(4):1671

    CAS  Google Scholar 

  4. Waks AG, Winer EP (2019) Breast cancer treatment: a review. JAMA 321(3):288–300

    Article  CAS  PubMed  Google Scholar 

  5. Singhai NJ, Ramteke S (2020) CNTs mediated CD44 targeting; a paradigm shift in drug delivery for breast cancer. Genes Dis 7(2):205–216

    Article  Google Scholar 

  6. Hill A, McFarlane S, Mulligan K, Gillespie H, Draffin J, Trimble A et al (2006) Cortactin underpins CD44-promoted invasion and adhesion of breast cancer cells to bone marrow endothelial cells. Oncogene 25(45):6079–6091

    Article  CAS  PubMed  Google Scholar 

  7. Mehralizadeh H, Nazari A, Oruji F, Roostaie M, Hosseininozari G, Yazdani O, Esbati R, Roudini K (2023 May) Cytokine sustained delivery for cancer therapy; special focus on stem cell-and biomaterial-based delivery methods. Pathology-Research Pract 9:154528

  8. Yu S, Chen Y, Li X, Gao Z, Liu G (2017) Chitosan nanoparticle-delivered siRNA reduces CXCR4 expression and sensitizes breast cancer cells to cisplatin. Biosci Rep 37(3):BSR20170122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ngamcherdtrakul W, Yantasee W (2019) siRNA therapeutics for breast cancer: recent efforts in targeting metastasis, drug resistance, and immune evasion. Transl Res 214:105–120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Yu C, Luan Y, Wang Z, Zhao J, Xu C (2017) Suppression of TAFI by siRNA inhibits invasion and migration of breast cancer cells. Mol Med Rep 16(3):3469–3474

    Article  CAS  PubMed  Google Scholar 

  11. Isazadeh H, Oruji F, Shabani S, Behroozi J, Nasiri H, Isazadeh A, Akbari M (2023) Advances in siRNA delivery approaches in cancer therapy: challenges and opportunities. Mol Biol Rep 50(11):9529–9543

    Article  CAS  PubMed  Google Scholar 

  12. Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H et al (2011) The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med 17(2):211–215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Liu X, Taftaf R, Kawaguchi M, Chang Y-F, Chen W, Entenberg D et al (2019) Homophilic CD44 interactions mediate tumor cell aggregation and polyclonal metastasis in patient-derived breast cancer models. Cancer Discov 9(1):96��113

    Article  PubMed  Google Scholar 

  14. Rimawi MF, Schiff R, Osborne CK (2015) Targeting HER2 for the treatment of breast cancer. Annu Rev Med. ;66

  15. Petrelli F, Barni S (2012) Role of HER2-neu as a prognostic factor for survival and relapse in pT1a–bN0M0 breast cancer: a systematic review of the literature with a pooled-analysis. Med Oncol 29(4):2586–2593

    Article  CAS  PubMed  Google Scholar 

  16. Al-Othman N, Ahram M, Alqaraleh M (2019) Role of androgen and microRNA in triple-negative breast cancer. Breast Dis. (Preprint):1–13

  17. Waugh DJ, McClatchey A, Montgomery N, McFarlane S (2009) Adhesion and penetration: two sides of CD44 signal transduction cascades in the context of cancer cell metastasis. Hyaluronan in Cancer Biology: Elsevier; pp. 109 – 25

  18. Orian-Rousseau V, Chen L, Sleeman JP, Herrlich P, Ponta H (2002) CD44 is required for two consecutive steps in HGF/c-Met signaling. Genes Dev 16(23):3074–3086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Zhao Z, Li Y, Liu H, Jain A, Patel PV, Cheng K (2020) Co-delivery of IKBKE siRNA and cabazitaxel by hybrid nanocomplex inhibits invasiveness and growth of triple-negative breast cancer. Sci Adv 6(29):eabb0616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Diebolder P, Mpoy C, Scott J, Huynh TT, Fields R, Spitzer D et al (2020) Preclinical evaluation of an Engineered scFv-Fc Targeting Human CD44. J Nucl Med. :jnumed. 120.249557.

  21. Suh JS, Lee HJ, Nam H, Jo BS, Lee DW, Kim J-H et al (2017) Control of cancer stem cell like population by intracellular target identification followed by the treatment with peptide-siRNA complex. Biochem Biophys Res Commun 491(3):827–833

    Article  CAS  PubMed  Google Scholar 

  22. Wang L, Zuo X, Xie K, Wei D (2018) The role of CD44 and cancer stem cells. cancer stem cells: Springer; pp. 31–42

  23. Zhang H, Brown RL, Wei Y, Zhao P, Liu S, Liu X et al (2019) CD44 splice isoform switching determines breast cancer stem cell state. Genes Dev 33(3–4):166–179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Wang X, Cheng K, Zhang G, Jia Z, Yu Y, Guo J et al (2020) Enrichment of CD44 in Exosomes from breast Cancer cells treated with Doxorubicin promotes Chemoresistance. Front Oncol 10:960

    Article  PubMed  PubMed Central  Google Scholar 

  25. Zhong Y, Zhang J, Cheng R, Deng C, Meng F, Xie F et al (2015) Reversibly crosslinked hyaluronic acid nanoparticles for active targeting and intelligent delivery of doxorubicin to drug resistant CD44 + human breast tumor xenografts. J Controlled Release 205:144–154

    Article  CAS  Google Scholar 

  26. Ryoo I-g, Choi B-h, Ku S-K, Kwak M-K (2018) High CD44 expression mediates p62-associated NFE2L2/NRF2 activation in breast cancer stem cell-like cells: implications for cancer stem cell resistance. Redox Biol 17:246–258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Shabani S, Moghadam MF, Gargari SL (2021) Isolation and characterization of a novel GRP78-specific single-chain variable fragment (scFv) using ribosome display method. Med Oncol 38(9):115

    Article  CAS  PubMed  Google Scholar 

  28. Gupta N, Jung K, Wu C, Alshareef A, Alqahtani H, Damaraju S et al (2017) High myc expression and transcription activity underlies intra-tumoral heterogeneity in triple-negative breast cancer. Oncotarget 8(17):28101

    Article  PubMed  PubMed Central  Google Scholar 

  29. Liu B-Q, Zhang S, Li S, An M-X, Li C, Yan J et al (2017) BAG3 promotes stem cell-like phenotype in breast cancer by upregulation of CXCR4 via interaction with its transcript. Cell Death Dis 8(7):e2933–e

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. An H, Kim JY, Oh E, Lee N, Cho Y, Seo JH (2015) Salinomycin promotes anoikis and decreases the CD44+/CD24-stem-like population via inhibition of STAT3 activation in MDA-MB-231 cells. PLoS ONE 10(11):e0141919

    Article  PubMed  PubMed Central  Google Scholar 

  31. Cheng C-C, Shi L-H, Wang X-J, Wang S-X, Wan X-Q, Liu S-R et al (2018) Stat3/Oct-4/c-Myc signal circuit for regulating stemness-mediated doxorubicin resistance of triple-negative breast cancer cells and inhibitory effects of WP1066. Int J Oncol 53(1):339–348

    CAS  PubMed  Google Scholar 

  32. Hashemi A, Bigdeli R, Shahnazari M, Oruji F, Fattahi S, Panahnejad E, Ghadri A, Movahedi-Asl E, Mahdavi-Ourtakand M, Asgary V, Baghbani-Arani F (2021) Evaluation of inflammasome activation in peripheral blood mononuclear cells of hemodialysis treated patients with glomerulonephritis. Iran J Pharm Research: IJPR 20(3):609

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Ling L-j, Shui W, Liu X-a, Shen E-c, Qiang D, Chao L et al (2008) A novel mouse model of human breast cancer stem-like cells with high CD44 + CD24˜/lower phenotype metastasis to human bone. Chin Med J 121(20):1980–1986

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank the Immunology Research Center, Tabriz University of Medical Sciences, for their support.

Funding

This study was supported by Tabriz University of Medical Sciences, Tabriz, Iran.

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Authors and Affiliations

Authors

Contributions

SGD and BB conceived and designed research. SGD, SN, and EB conducted experiments. NM and TJ contributed new reagents or analytical tools. SN and EB analyzed data. SGD wrote the manuscript. All authors read and approved the manuscript and all data were generated in-house and that no paper mill was used.

Corresponding author

Correspondence to Behzad Baradaran.

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Ethical approval

All experiments and procedures were conducted in compliance with the ethical principles of Tabriz University of Medical Science, Tabriz, Iran and approved by the regional ethical committee for medical research (Ethical code: TBZMED.REC.1396.841).

Competing Interests

All authors declare they have no financial interests.

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Dehbokri, S.G., Noorolyai, S., Baghbani, E. et al. Effects of CD44 siRNA on inhibition, survival, and apoptosis of breast cancer cell lines (MDA-MB-231 and 4T1). Mol Biol Rep 51, 646 (2024). https://doi.org/10.1007/s11033-024-09572-9

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