Dual Regulation of miR-34a and Notch Signaling in Triple-Negative Breast Cancer by Antibody/miRNA Nanocarriers

Valcourt, Danielle M.; Day, Emily S.

doi:10.1016/j.omtn.2020.06.003

Cited by 40 publications

(20 citation statements)

References 48 publications

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“…Here, the Notch1 antibodies had a dual role and did not only serve the purpose of being the targeting moiety, but also enabled suppression of Notch signaling. Additionally, the performed in vitro experiments showed regulation of miR-34a targets as well as induction of senescence and reduction of cell proliferation and migration [ 180 ]. Taken together, the developed systems for co-delivery show high potential to overcome chemotherapy resistance.…”

Section: Combination With Cancer Therapy To Counteract Mir-mediatementioning

confidence: 99%

Therapeutic Targeting of MicroRNAs in the Tumor Microenvironment

Raue

Frank

Syed

et al. 2021

IJMS

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The tumor-microenvironment (TME) is an amalgamation of various factors derived from malignant cells and infiltrating host cells, including cells of the immune system. One of the important factors of the TME is microRNAs (miRs) that regulate target gene expression at a post transcriptional level. MiRs have been found to be dysregulated in tumor as well as in stromal cells and they emerged as important regulators of tumorigenesis. In fact, miRs regulate almost all hallmarks of cancer, thus making them attractive tools and targets for novel anti-tumoral treatment strategies. Tumor to stroma cell cross-propagation of miRs to regulate protumoral functions has been a salient feature of the TME. MiRs can either act as tumor suppressors or oncogenes (oncomiRs) and both miR mimics as well as miR inhibitors (antimiRs) have been used in preclinical trials to alter cancer and stromal cell phenotypes. Owing to their cascading ability to regulate upstream target genes and their chemical nature, which allows specific pharmacological targeting, miRs are attractive targets for anti-tumor therapy. In this review, we cover a recent update on our understanding of dysregulated miRs in the TME and provide an overview of how these miRs are involved in current cancer-therapeutic approaches from bench to bedside.

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Section: Combination With Cancer Therapy To Counteract Mir-mediatementioning

confidence: 99%

Therapeutic Targeting of MicroRNAs in the Tumor Microenvironment

Raue

Frank

Syed

et al. 2021

IJMS

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“…TQ also halts the PI3K/AKT signaling pathway by upregulating PTEN, thus interfering with GSK-3β activity, enhancing β-catenin degradation, and decreasing MMP-9 and MMP-2 levels in esophageal cancer cells (Eca109 cells) [ 83 ]. MicroRNA-34a (miR-34a) expression is vital to cancer development and metastasis [ 90 ], and its expression is reduced by TQ in human metastatic breast cancers (MBC) compared to normal breast tissues [ 91 ]. Altogether, microRNA-34a can act as therapy either alone or in combination with TQ, and synergize therapeutic potential [ 92 ].…”

Section: Neoplasm and Its Pathogenesismentioning

confidence: 99%

Recent Findings on Thymoquinone and Its Applications as a Nanocarrier for the Treatment of Cancer and Rheumatoid Arthritis

et al. 2021

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Cancer causes a considerable amount of mortality in the world, while arthritis is an immunological dysregulation with multifactorial pathogenesis including genetic and environmental defects. Both conditions have inflammation as a part of their pathogenesis. Resistance to anticancer and disease-modifying antirheumatic drugs (DMARDs) happens frequently through the generation of energy-dependent transporters, which lead to the expulsion of cellular drug contents. Thymoquinone (TQ) is a bioactive molecule with anticancer as well as anti-inflammatory activities via the downregulation of several chemokines and cytokines. Nevertheless, the pharmacological importance and therapeutic feasibility of thymoquinone are underutilized due to intrinsic pharmacokinetics, including short half-life, inadequate biological stability, poor aqueous solubility, and low bioavailability. Owing to these pharmacokinetic limitations of TQ, nanoformulations have gained remarkable attention in recent years. Therefore, this compilation intends to critically analyze recent advancements in rheumatoid arthritis and cancer delivery of TQ. This literature search revealed that nanocarriers exhibit potential results in achieving targetability, maximizing drug internalization, as well as enhancing the anti-inflammatory and anticancer efficacy of TQ. Additionally, TQ-NPs (thymoquinone nanoparticles) as a therapeutic payload modulated autophagy as well as enhanced the potential of other drugs when given in combination. Moreover, nanoformulations improved pharmacokinetics, drug deposition, using EPR (enhanced permeability and retention) and receptor-mediated delivery, and enhanced anti-inflammatory and anticancer properties. TQ’s potential to reduce metal toxicity, its clinical trials and patents have also been discussed.

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“…Abnormal expression of miRNAs has been documented to be associated with inflammation and tumor progression. 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 miR-4721 was first identified in 2011, 11 yet knowledge about the regulatory function and its role in carcinogenesis is still lacking.…”

Section: Introductionmentioning

confidence: 99%

miR-4721, Induced by EBV-miR-BART22, Targets GSK3β to Enhance the Tumorigenic Capacity of NPC through the WNT/β-catenin Pathway

Tang

Chen

et al. 2020

Molecular Therapy - Nucleic Acids

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Nasopharyngeal carcinoma (NPC) is prevalent in East and Southeast Asia. In a previous study, Epstein-Barr virus (EBV)-miR-BART22 induces tumor metastasis and stemness and is significantly involved in NPC progression. In the present study, we observed that miR-4721 is induced by EBV-miR-BART22 through phosphatidylinositol 3-kinase (PI3K)/AKT/c-JUN/Sp1 signaling to promote its transcription. In a subsequent study, we observed that miR-4721 serves as a potential oncogenic factor promoting NPC cell cycle progression and cell proliferation in vitro and in vivo . Mechanism analysis indicated that miR-4721 directly targetes GSK3β and reduces its expression, which therefore elevates β-catenin intra-nuclear aggregation and activates its downstream cell cycle factors, including CCND1 and c-MYC. In clinical samples, miR-4721 and GSK3β are respectively observed to be upregulated and downregulated in NPC progression. Elevated expression of miR-4721 is positively associated with clinical progression and poor prognosis. Our study first demonstrated that miR-4721 as an oncogene is induced by EBV-miR-BART22 via modulating PI3K/AKT/c-JUN/Sp1 signaling to target GSK3β, which thus activates the WNT/β-catenin-stimulated cell cycle signal and enhances the tumorigenic capacity in NPC. miR-4721 may be a potential biomarker or therapeutic target in NPC treatment in the future.

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Dual Regulation of miR-34a and Notch Signaling in Triple-Negative Breast Cancer by Antibody/miRNA Nanocarriers

Cited by 40 publications

References 48 publications

Therapeutic Targeting of MicroRNAs in the Tumor Microenvironment

Therapeutic Targeting of MicroRNAs in the Tumor Microenvironment

Recent Findings on Thymoquinone and Its Applications as a Nanocarrier for the Treatment of Cancer and Rheumatoid Arthritis

miR-4721, Induced by EBV-miR-BART22, Targets GSK3β to Enhance the Tumorigenic Capacity of NPC through the WNT/β-catenin Pathway

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