A Comprehensive Review of Cancer MicroRNA Therapeutic Delivery Strategies

Forterre, Alexis V.; Komuro, Hiroaki; Aminova, Shakhlo; Harada, Masahiko

doi:10.3390/cancers12071852

Cited by 177 publications

(143 citation statements)

References 169 publications

(206 reference statements)

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“…MicroRNA is emerging as a next generation cancer treatment [41][42][43][44]. Studies showed that miR-1291 had anti-tumor effects in multiple cancers including renal cancer, esophagus cancer, pancreatic cancer, and prostate cancer [31][32][33][34].…”

Section: Discussionmentioning

confidence: 99%

Anti-tumor effect of miR-1291 in colorectal cancer

Wang

Hirose

Yokoyama

et al. 2020

Preprint

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Background: MiR-1291 has an anti-tumor effect in carcinoma of kidney, esophagus, pancreas, and prostate. However, it’s role in colorectal cancer (CRC) has not been elucidated.Methods: In this study, we explored the effect of miR-1291 in CRC cells (HCT116, DLD-1, and HT29) in vitro, and performed a tumor growth inhibitory assay in a mouse therapeutic model using DLD-1 cells. Flow cytometric analysis and Western blotting were performed to examine a role of miR-1291 in cell cycle regulation. We performed luciferase reporter assay to verify the interaction between DCLK1 and miR-1291 in HCT116 cells. Cancer stemness was evaluated by identifying the expression of BMI1 and CD133, as well as performing sphere formation assay. Results: We found that miR-1291 significantly suppressed the proliferation, invasion, cell mobility, and colony formation capability of CRC cell lines. MiR-1291 caused altered expression of the cell cycle-regulatory proteins, representatively CDK inhibitors p21WAF1/CIP1 and p27KIP1 or CDK4. Moreover, intravenous administration of miR-1291 loaded on the super carbonate apatite delivery system significantly inhibited a tumor growth in the DLD-1 xenograft mouse model. A luciferase reporter assay showed that miR-1291 directly bound the 3’ UTR sequence of DCLK1 and suppressed its expression at both the mRNA and protein levels in HCT116 expressing the DCLK1 protein. In addition, miR-1291 suppressed cancer stem cell (CSC) markers BMI1 and CD133 as well as sphere formation ability in HCT116 cells. Conclusions: Taken together, these findings indicate that miR-1291 has an anti-tumor effect by modulating multiple functions, including cell cycle, invasiveness, and cancer stemness. Our data suggest that miR-1291 could be a promising nucleic acid medicine against CRC.

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Section: Discussionmentioning

confidence: 99%

Anti-tumor effect of miR-1291 in colorectal cancer

Wang

Hirose

Yokoyama

et al. 2020

Preprint

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“…Further studies regarding the role of CaSR and its downstream signaling pathways in HL-1 cells are required. Although the HAp-based vector used here has a low transfection efficiency, it has already been used as a gene delivery system in in vivo cancer research experiments [38]. Furthermore, this system might be useful for increasing the knowledge about cellular uptake mechanisms in heart cells, which are difficult to transfect.…”

Section: Discussionmentioning

confidence: 99%

Cardiomyocyte uptake mechanism of a hydroxyapatite nanoparticle mediated gene delivery system

Komuro¹,

Yamazoe²,

Nozaki³

et al. 2020

Beilstein J. Nanotechnol.

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Gene therapy has been explored as a future alternative for treating heart disease. Among several gene delivery systems aimed at penetrating specific target cells, we focused on safe and non-viral gene delivery materials with a high transfection efficiency. Although various techniques have been developed, the mechanisms underlying the cellular uptake of gene delivery materials have not yet been sufficiently studied in cardiomyocytes. The aim of this study was to determine how hydroxyapatite (HAp) nanoparticles contribute to the delivery of plasmid DNA (pDNA) into cardiomyocytes. We fabricated HAp nanoparticles using the water-in-oil (W/O) emulsion method and used these nanoparticles as the delivery vector for transfecting cardiomyocyte-derived HL-1 cells. HAp exhibited particles on the nanoscale and with a low cytotoxicity in HL-1 cells. The transfection assay performed with several endocytosis inhibitors suggested that the HAp/pDNA complexes were internalized by HL-1 cells through macropinocytosis. Furthermore, this HL-1 cell uptake was generated in response to HAp stimulation. Thus, HAp is a positive regulator of macropinocytosis in HL-1 cells and a good system for gene delivery in cardiomyocytes.

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“…MiRNAs seem to have the potential for therapeutic use [ 554 , 555 , 556 ]. However, the first clinical trials did not live up to expectations.…”

Section: Challenges For the Use Of Mirnas In Clinical Oncologymentioning

confidence: 99%

Regulators at Every Step—How microRNAs Drive Tumor Cell Invasiveness and Metastasis

Grzywa

Klicka

Włodarski

2020

Cancers

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Tumor cell invasiveness and metastasis are the main causes of mortality in cancer. Tumor progression is composed of many steps, including primary tumor growth, local invasion, intravasation, survival in the circulation, pre-metastatic niche formation, and metastasis. All these steps are strictly controlled by microRNAs (miRNAs), small non-coding RNA that regulate gene expression at the post-transcriptional level. miRNAs can act as oncomiRs that promote tumor cell invasion and metastasis or as tumor suppressor miRNAs that inhibit tumor progression. These miRNAs regulate the actin cytoskeleton, the expression of extracellular matrix (ECM) receptors including integrins and ECM-remodeling enzymes comprising matrix metalloproteinases (MMPs), and regulate epithelial–mesenchymal transition (EMT), hence modulating cell migration and invasiveness. Moreover, miRNAs regulate angiogenesis, the formation of a pre-metastatic niche, and metastasis. Thus, miRNAs are biomarkers of metastases as well as promising targets of therapy. In this review, we comprehensively describe the role of various miRNAs in tumor cell migration, invasion, and metastasis.

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A Comprehensive Review of Cancer MicroRNA Therapeutic Delivery Strategies

Cited by 177 publications

References 169 publications

Anti-tumor effect of miR-1291 in colorectal cancer

Anti-tumor effect of miR-1291 in colorectal cancer

Cardiomyocyte uptake mechanism of a hydroxyapatite nanoparticle mediated gene delivery system

Regulators at Every Step—How microRNAs Drive Tumor Cell Invasiveness and Metastasis

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