A Systematic Review on the Therapeutic Potentiality of PD-L1-Inhibiting MicroRNAs for Triple-Negative Breast Cancer: Toward Single-Cell Sequencing-Guided Biomimetic Delivery

The programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) is a well-established inhibitory immune checkpoint axis in triple-negative breast cancer (TNBC). Growing evidence indicates that tumoral PD-L1 can lead to TNBC development. Although conventional immune checkpoint inhibitors have improved TNBC patients’ prognosis, their effect is mainly focused on improving anti-tumoral immune responses without substantially regulating oncogenic signaling pathways in tumoral cells. Moreover, the conventional immune checkpoint inhibitors cannot impede the de novo expression of oncoproteins, like PD-L1, in tumoral cells. Accumulating evidence has indicated that the restoration of specific microRNAs (miRs) can downregulate tumoral PD-L1 and inhibit TNBC development. Since miRs can target multiple mRNAs, miR-based gene therapy can be an appealing approach to inhibit the de novo expression of oncoproteins, like PD-L1, restore anti-tumoral immune responses, and regulate various intracellular singling pathways in TNBC. Therefore, we conducted the current systematic review based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) to provide a comprehensive and unbiased synthesis of currently available evidence regarding the effect of PD-L1-inhibiting miRs restoration on TNBC development and tumor microenvironment. For this purpose, we systematically searched the Cochrane Library, Embase, Scopus, PubMed, ProQuest, Web of Science, Ovid, and IranDoc databases to obtain the relevant peer-reviewed studies published before 25 May 2021. Based on the current evidence, the restoration of miR-424-5p, miR-138-5p, miR-570-3p, miR-200c-3p, miR-383-5p, miR-34a-5p, miR-3609, miR-195-5p, and miR-497-5p can inhibit tumoral PD-L1 expression, transform immunosuppressive tumor microenvironment into the pro-inflammatory tumor microenvironment, inhibit tumor proliferation, suppress tumor migration, enhance chemosensitivity of tumoral cells, stimulate tumor apoptosis, arrest cell cycle, repress the clonogenicity of tumoral cells, and regulate various oncogenic signaling pathways in TNBC cells. Concerning the biocompatibility of biomimetic carriers and the valuable insights provided by the single-cell sequencing technologies, single-cell sequencing-guided biomimetic delivery of these PD-L1-inhibiting miRs can decrease the toxicity of traditional approaches, increase the specificity of miR-delivery, enhance the efficacy of miR delivery, and provide the affected patients with personalized cancer therapy.

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References

90

[1]

Yersal "Biological subtypes of breast cancer: Prognostic and therapeutic implications" World J. Clin. Oncol. (2014) 10.5306/wjco.v5.i3.412

[2]

Viale "Pathological and molecular diagnosis of triple-negative breast cancer: A clinical perspective" Ann. Oncol. (2012)

[3]

Pareja "Triple-negative breast cancer: The importance of molecular and histologic subtyping, and recognition of low-grade variants" NPJ Breast Cancer (2016) 10.1038/npjbcancer.2016.36

[4]

Hosseinkhani, N., Derakhshani, A., Kooshkaki, O., Abdoli Shadbad, M., Hajiasgharzadeh, K., Baghbanzadeh, A., Safarpour, H., Mokhtarzadeh, A., Brunetti, O., and Yue, S.C. (2020). Immune Checkpoints and CAR-T Cells: The Pioneers in Future Cancer Therapies?. Int. J. Mol. Sci., 21. 10.3390/ijms21218305

[5]

Lotfinejad, P., Asghari Jafarabadi, M., Abdoli Shadbad, M., Kazemi, T., Pashazadeh, F., Sandoghchian Shotorbani, S., Jadidi Niaragh, F., Baghbanzadeh, A., Vahed, N., and Silvestris, N. (2020). Prognostic role and clinical significance of tumor-infiltrating lymphocyte (TIL) and programmed death ligand 1 (PD-L1) expression in triple-negative breast cancer (TNBC): A systematic review and meta-analysis study. Diagnostics, 10. 10.3390/diagnostics10090704

[6]

Huang "PDL1 And LDHA act as ceRNAs in triple negative breast cancer by regulating miR-34a" J. Exp. Clin. Cancer Res. (2017) 10.1186/s13046-017-0593-2

[7]

Mediratta, K., El-Sahli, S., D’Costa, V., and Wang, L. (2020). Current progresses and challenges of immunotherapy in triple-negative breast cancer. Cancers, 12. 10.3390/cancers12123529

[8]

Lotfinejad "PD-L1 silencing inhibits triple-negative breast cancer development and upregulates T-cell-induced pro-inflammatory cytokines" Biomed. Pharmacother. (2021) 10.1016/j.biopha.2021.111436

[9]

Cui "Circulating microRNAs in cancer: Potential and challenge" Front. Genet. (2019) 10.3389/fgene.2019.00626

[10]

Dastmalchi, N., Safaralizadeh, R., SM, B.K., Sam, M.R., Latifi-Navid, S., Hussen, B.M., and Baradaran, B. An Updated Review of the Cross-talk between MicroRNAs and Epigenetic Factors in Cancers. Curr. Med. Chem., 2021. 10.2174/0929867328666210514125955

[11]

Ahangar, N.K., Hemmat, N., Khalaj-Kondori, M., Shadbad, M.A., Sabaie, H., Mokhtarzadeh, A., Alizadeh, N., Derakhshani, A., Baghbanzadeh, A., and Dolatkhah, K. (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. 10.3390/ijms22052652

[12]

Zhou, Y., Yamamoto, Y., Takeshita, F., Yamamoto, T., Xiao, Z., and 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. 10.3390/ijms22020844

[13]

Wang "Protective effect of hsa-miR-570-3p targeting CD274 on triple negative breast cancer by blocking PI3K/AKT/mTOR signaling pathway" Kaohsiung J. Med. Sci. (2020) 10.1002/kjm2.12212

[14]

Moher, D., Liberati, A., Tetzlaff, J., Altman, D.G., and Group, P. (2009). Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med., 6. 10.1371/journal.pmed.1000097

[15]

Chavez "Triple negative breast cancer cell lines: One tool in the search for better treatment of triple negative breast cancer" Breast Dis. (2010) 10.3233/bd-2010-0307

[16]

Hooijmans, C.R., Rovers, M.M., de Vries, R.B., Leenaars, M., Ritskes-Hoitinga, M., and Langendam, M.W. (2014). SYRCLE’s risk of bias tool for animal studies. BMC Med. Res. Methodol., 14. 10.1186/1471-2288-14-43

[17]

Raj "Assessing the effect of human mesenchymal stem cell-derived conditioned media on human cancer cell lines: A systematic review" Tissue Cell (2021) 10.1016/j.tice.2021.101505

[18]

Peng "Identification of CTLA-4 associated with tumor microenvironment and competing interactions in triple negative breast cancer by co-expression network analysis" J. Cancer (2020) 10.7150/jca.46301

[19]

Qattan, A., Al-Tweigeri, T., Alkhayal, W., Suleman, K., Tulbah, A., and Amer, S. (2021). Clinical Identification of Dysregulated Circulating microRNAs and Their Implication in Drug Response in Triple Negative Breast Cancer (TNBC) by Target Gene Network and Meta-Analysis. Genes, 12. 10.3390/genes12040549

[20]

Liu, Z., Mi, M., Li, X., Zheng, X., Wu, G., and Zhang, L. (2019). lncRNA OSTN-AS1 May Represent a Novel Immune-Related Prognostic Marker for Triple-Negative Breast Cancer Based on Integrated Analysis of a ceRNA Network. Front. Genet., 10. 10.3389/fgene.2019.00850

[21]

Naba "Doxorubicin inhibits miR-140 expression and upregulates PD-L1 expression in HCT116 cells, opposite to its effects on MDA-MB-231 cells" Turk. J. Biol. (2020)

[22]

Yang "Ethyl Acetate Fraction from Hedyotis diffusa plus Scutellaria barbata Exerts Anti-Breast Cancer Effect via miR-200c-PDE7B/PD-L1-AKT/MAPK Axis" Evid.-Based Complement. Altern. Med. (2020) 10.1155/2020/3587095

[23]

Noman, M.Z., Janji, B., Abdou, A., Hasmim, M., Terry, S., Tan, T.Z., Mami-Chouaib, F., Thiery, J.P., and Chouaib, S. (2017). The immune checkpoint ligand PD-l1 is upregulated in EMT-activated human breast cancer cells by a mechanism involving ZEB-1 and miR-200. Oncoimmunology, 6. 10.1080/2162402x.2016.1263412

[24]

Zhang, M., Wang, N., Song, P., Fu, Y., Ren, Y., Li, Z., and Wang, J. (2020). LncRNA GATA3-AS1 facilitates tumour progression and immune escape in triple-negative breast cancer through destabilization of GATA3 but stabilization of PD-L1. Cell Prolif., 53. 10.1111/cpr.12855

[25]

Nafea "LncRNA HEIH/miR-939-5p interplay modulates triple-negative breast cancer progression through NOS2-induced nitric oxide production" J. Cell. Physiol. (2021) 10.1002/jcp.30234

[26]

Youness "Targeting hydrogen sulphide signaling in breast cancer" J. Adv. Res. (2021) 10.1016/j.jare.2020.07.006

[27]

Hamed, M.M., Handoussa, H., Hussein, N.H., Eissa, R.A., Abdel-Aal, L.K., and El Tayebi, H.M. (2021). Oleuropin controls miR-194/XIST/PD-L1 loop in triple negative breast cancer: New role of nutri-epigenetics in immune-oncology. Life Sci., 277. 10.1016/j.lfs.2021.119353

[28]

Yao "Endoplasmic reticulum stress-induced exosomal miR-27a-3p promotes immune escape in breast cancer via regulating PD-L1 expression in macrophages" J. Cell. Mol. Med. (2020) 10.1111/jcmm.15367

[29]

Rogers "Reversal of triple-negative breast cancer EMT by miR-200c decreases tryptophan catabolism and a program of immunosuppression" Mol. Cancer Res. (2019) 10.1158/1541-7786.mcr-18-0246

[30]

Dastmalchi "MicroRNA-424-5p enhances chemosensitivity of breast cancer cells to Taxol and regulates cell cycle, apoptosis, and proliferation" Mol. Biol. Rep. (2021) 10.1007/s11033-021-06193-4

[31]

Soufiani "Tumor Microenvironment Changing through Application of MicroRNA-34a Related Mesenchymal Stem Cells Conditioned Medium: Modulation of Breast Cancer Cells toward Non-aggressive Behavior" Iran. J. Allergy Asthma Immunol. (2021)

[32]

Rasoolnezhad "MiRNA-138–5p: A strong tumor suppressor targeting PD-L-1 inhibits proliferation and motility of breast cancer cells and induces apoptosis" Eur. J. Pharmacol. (2021) 10.1016/j.ejphar.2021.173933

[33]

Peng "(-)-Sativan Inhibits Tumor Development and Regulates miR-200c/PD-L1 in Triple Negative Breast Cancer Cells" Front Pharmacol. (2020) 10.3389/fphar.2020.00251

[34]

Dastmalchi "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. (2020) 10.1016/j.lfs.2020.118239

[35]

Azarbarzin, S., Hosseinpour-Feizi, M.A., Banan Khojasteh, S.M., Baradaran, B., and Safaralizadeh, R. (2021). MicroRNA -383-5p restrains the proliferation and migration of breast cancer cells and promotes apoptosis via inhibition of PD-L1. Life Sci., 267. 10.1016/j.lfs.2020.118939

[36]

Zhao "Prognostic value of PD-L1 for invasive breast cancer and its miR-34a-related mechanism of regulation" Int. J. Clin. Exp. Med. (2019)

[37]

Li "miR3609 sensitizes breast cancer cells to adriamycin by blocking the programmed death-ligand 1 immune checkpoint" Exp. Cell Res. (2019) 10.1016/j.yexcr.2019.03.025

[38]

Yang "miR-195/miR-497 regulate CD274 expression of immune regulatory ligands in triple-negative breast cancer" J. Breast Cancer (2018) 10.4048/jbc.2018.21.e60

[39]

(2021, March 07). FDA Grants Accelerated Approval to Pembrolizumab for Locally Recurrent Unresectable or Metastatic Triple Negative Breast Cancer, Available online: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pembrolizumab-locally-recurrent-unresectable-or-metastatic-triple.

[40]

Wang "miR-424-5p regulates cell proliferation, migration and invasion by targeting doublecortin-like kinase 1 in basal-like breast cancer" Biomed. Pharmacother. (2018) 10.1016/j.biopha.2018.03.018

[41]

Xie "MicroRNA-424 serves an anti-oncogenic role by targeting cyclin-dependent kinase 1 in breast cancer cells" Oncol. Rep. (2018)

[42]

Zhao "MicroRNA-138-5p inhibits cell migration, invasion and EMT in breast cancer by directly targeting RHBDD1" Breast Cancer (2019) 10.1007/s12282-019-00989-w

[43]

Li "Inhibition of the proliferation and migration of triple negative breast cancer cells by targeting ezh2 using MIR-138-5P" Acta Med. Mediterr. (2021)

[44]

Li "MiR-138-5p targeting LIMK1 suppresses breast cancer cell proliferation and motility" RSC Adv. (2017) 10.1039/c7ra09042k

[45]

Ren "microRNA-200c downregulates XIAP expression to suppress proliferation and promote apoptosis of triple-negative breast cancer cells" Mol. Med. Rep. (2014) 10.3892/mmr.2014.2222

[46]

Zhang "LncRNA XIST promotes chemoresistance of breast cancer cells to doxorubicin by sponging miR-200c-3p to upregulate ANLN" Clin. Exp. Pharmacol. Physiol. (2020) 10.1111/1440-1681.13307

[47]

Chang "miR-200c inhibits metastasis of breast cancer cells by targeting HMGB1" J. Huazhong Univ. Sci. Technol. Med. Sci. (2014) 10.1007/s11596-014-1259-3

[48]

Berber "miR-205 and miR-200c: Predictive Micro RNAs for Lymph Node Metastasis in Triple Negative Breast Cancer" J. Breast Cancer (2014) 10.4048/jbc.2014.17.2.143

[49]

Zhang "MicroRNA-383-5p acts as a potential prognostic biomarker and an inhibitor of tumor cell proliferation, migration, and invasion in breast cancer" Cancer Biomark. (2020) 10.3233/cbm-190704

[50]

Tian "LINC00096 promotes the proliferation and invasion by sponging miR-383-5p and regulating RBM3 expression in triple-negative breast cancer" Onco Targets Ther. (2019) 10.2147/ott.s229659

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Details

Published: Aug 04, 2021
Vol/Issue: 12(8)
Pages: 1206
License: View

Authors

M

Mahdi Abdoli Shadbad

Research Center for Evidence-Based Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz 5166614766, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 5165665811, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz 5165665811, Iran

S

Sahar Safaei

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 5165665811, Iran

O

Oronzo Brunetti

Medical Oncology Unit, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy

A

Afshin Derakhshani

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 5165665811, Iran; Laboratory of Experimental Pharmacology, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy

P

Parisa Lotfinejad

Research Center for Evidence-Based Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz 5166614766, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 5165665811, Iran

A

Ahad Mokhtarzadeh

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 5165665811, Iran

N

Nima Hemmat

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 5165665811, Iran

V

Vito Racanelli

Department of Biomedical Sciences and Human Oncology, Unit of Internal Medicine and Clinical Oncology, University of Bari “Aldo Moro”, 70124 Bari, Italy

A

Antonio Giovanni Solimando

Medical Oncology Unit, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy; Department of Biomedical Sciences and Human Oncology, Unit of Internal Medicine and Clinical Oncology, University of Bari “Aldo Moro”, 70124 Bari, Italy

A

Antonella Argentiero

Medical Oncology Unit, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy

N

Nicola Silvestris

Medical Oncology Unit, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy; Department of Biomedical Sciences and Human Oncology, Unit of Internal Medicine and Clinical Oncology, University of Bari “Aldo Moro”, 70124 Bari, Italy

B

Behzad Baradaran

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 5165665811, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz 5166614766, Iran

Cite This Article

Mahdi Abdoli Shadbad, Sahar Safaei, Oronzo Brunetti, et al. (2021). A Systematic Review on the Therapeutic Potentiality of PD-L1-Inhibiting MicroRNAs for Triple-Negative Breast Cancer: Toward Single-Cell Sequencing-Guided Biomimetic Delivery. Genes, 12(8), 1206. https://doi.org/10.3390/genes12081206

A Systematic Review on the Therapeutic Potentiality of PD-L1-Inhibiting MicroRNAs for Triple-Negative Breast Cancer: Toward Single-Cell Sequencing-Guided Biomimetic Delivery

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