Sistematski pregled terapeutskog potencijala mikroRNA koje inhibiraju PD-L1 za trostruko negativan rak dojke: prema biomimetičkoj isporuci vođenoj sekvenciranjem jedne ćelije.
Genes
Sažetak istraživanja
Programirani ligand smrti 1 (PD-L1)/protein programirane ćelijske smrti 1 (PD-1) je dobro uspostavljena osa inhibitorne imunološke kontrolne tačke kod trostruko negativnog raka dojke (TNBC). Sve veći broj dokaza ukazuje da tumorski PD-L1 može dovesti do razvoja TNBC. Iako su konvencionalni inhibitori imunoloških kontrolnih tačaka poboljšali prognozu TNBC pacijenata, njihov učinak je uglavnom usmjeren na poboljšanje antitumorskih imunoloških odgovora bez suštinske regulacije onkogenih signalnih puteva u tumorskim stanicama. Štaviše, konvencionalni inhibitori imunološke kontrolne tačke ne mogu spriječiti de novo ekspresiju onkoproteina, poput PD-L1, u tumorskim stanicama. Nagomilani dokazi pokazuju da obnavljanje specifičnih mikroRNA (miR) može smanjiti regulaciju tumorskog PD-L1 i inhibirati razvoj TNBC. Budući da miR-ovi mogu ciljati više mRNA, genska terapija zasnovana na miR-u može biti privlačan pristup za inhibiciju de novo ekspresije onkoproteina, kao što je PD-L1, obnavljanje antitumorskih imunoloških odgovora i regulaciju različitih intracelularnih puteva izdvajanja u TNBC. Stoga smo sproveli trenutni sistematski pregled zasnovan na preferiranim stavkama izvještavanja za sistematske preglede i meta-analize (PRISMA) kako bismo pružili sveobuhvatnu i nepristrasnu sintezu trenutno dostupnih dokaza u vezi s efektom restauracije miR-a koji inhibira PD-L1 na razvoj TNBC i mikrookruženje tumora. U tu svrhu, sistematski smo pretraživali Cochrane Library, Embase, Scopus, PubMed, ProQuest, Web of Science, Ovid i IranDoc baze podataka kako bismo dobili relevantne recenzirane studije objavljene prije 25. maja 2021. Na osnovu trenutnih dokaza, restauracija miR-424-13p, miR-7p, 5p, 13p8 miR-200c-3p, miR-383-5p, miR-34a-5p, miR-3609, miR-195-5p i miR-497-5p mogu inhibirati tumorsku ekspresiju PD-L1, transformirati imunosupresivno tumorsko mikrookruženje u pro-inflamatorno tumorsko okruženje, pro-inflamatorni tumori, miR-195-5p i miR-497-5p. pojačavaju hemosenzitivnost tumorskih ćelija, stimulišu apoptozu tumora, zaustavljaju ćelijski ciklus, potiskuju klonogenost tumorskih ćelija i regulišu različite onkogene signalne puteve u TNBC ćelijama. Što se tiče biokompatibilnosti biomimetičkih nosača i vrijednih uvida koje pružaju tehnologije jednoćelijskog sekvenciranja, biomimetička isporuka ovih miR-inhibirajućih PD-L1 može smanjiti toksičnost tradicionalnih pristupa, povećati specifičnost miR-isporuke, poboljšati osobnu isporuku miR-a i poboljšati osobnu terapiju kod pacijenata s rakom.
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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.
Izvorni podaci
- DOI
- 10.3390/genes12081206
- PMID
- 34440380
- PMCID
- PMC8391239
- Provjereno
- 2026-07-26
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