MicroRNA Targeting to Modulate Tumor Microenvironment

Frontiers in Oncology, Journal Year: 2016, Volume and Issue: 6

Published: Jan. 19, 2016

Communication between stromal cells and tumor initiates growth, angiogenesis, invasion, metastasis. Stromal include cancer-associated fibroblasts, tumor-associated macrophages, pericytes, endothelial cells, infiltrating immune cells. MicroRNAs (miRNAs) in the microenvironment have emerged as key players involved development of cancer its progression. miRNAs are small endogenous non-protein-coding RNAs that negatively regulate expression multiple target genes at post-transcriptional level thereby control many cellular processes. In this review, we provide a comprehensive overview dysregulated different their impact on regulation intercellular crosstalk microenvironment. We also discuss therapeutic significance potential to modulate Since miRNA delivery is quite challenging biggest hurdle for clinical translation therapeutics, review various non-viral systems can potentially be used targeting within

Language: Английский

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miRNA and Cancer

Elsevier eBooks, Journal Year: 2017, Volume and Issue: unknown, P. 27 - 46

Published: Nov. 28, 2017

Language: Английский

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Suppressing miR-21 activity in tumor-associated macrophages promotes an antitumor immune response

Journal of Clinical Investigation, Journal Year: 2019, Volume and Issue: 129(12), P. 5518 - 5536

Published: Nov. 10, 2019

microRNA-21 (miR-21) is the most commonly upregulated miRNA in solid tumors. This cancer-associated microRNA (oncomiR) regulates various downstream effectors associated with tumor pathogenesis during all stages of carcinogenesis. In this study, we analyzed function miR-21 noncancer cells microenvironment to further evaluate its contribution progression. We report that expression immune infiltrate, and particular macrophages, was responsible for promoting growth. Absence tumor- macrophages (TAMs), caused a global rewiring their transcriptional regulatory network skewed toward proinflammatory angiostatic phenotype. promoted an antitumoral response characterized by macrophage-mediated improvement cytotoxic T-cell responses through induction cytokines chemokines, including IL-12 C-X-C motif chemokine 10. These effects translated reduction neovascularization cell death led decreased Additionally, using carrier peptide pH (low) insertion peptide, were able target TAMs, which growth even under conditions where deficient cancer cells. Consequently, inhibition TAMs induced immunostimulatory activation potential therapeutic implications.

Language: Английский

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HLA-G 3′ untranslated region variants +3187G/G, +3196G/G and +3035T define diametrical clinical status and disease outcome in epithelial ovarian cancer

Scientific Reports, Journal Year: 2019, Volume and Issue: 9(1)

Published: April 1, 2019

Abstract Expression of the non-classical human leukocyte antigen-G (HLA-G) promotes cancer progression in various malignancies including epithelial ovarian (EOC). As single nucleotide polymorphisms (SNPs) HLA-G 3′ untranslated region (UTR) regulate expression, we investigated 3′UTR haplotypes arranged by SNPs healthy controls (n = 75) and primary EOC patients 79) determined soluble (sHLA-G) levels. Results were related to clinical status outcome. Although haplotype frequencies similar controls, (i) sHLA-G levels increased independent haplotype, (ii) homozygosity for UTR-1 or UTR-2 genotypes significantly associated with metastases formation presence circulating tumor cells before therapy, whereas (iii) UTR-5 UTR-7 a beneficial outcome regarding negative nodal status, early FIGO staging, improved overall survival. Lastly, (iv) ambivalent impact on aspects could be deduced specific 3′UTR: +3187G, +3196G +3035T alleles. Our results give evidence that even if genetic background is identical between certain have potential contribute diametrical status/outcome EOC.

Language: Английский

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The Role of Exosomal MicroRNAs in the Tumor Microenvironment of Breast Cancer

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(16), P. 3884 - 3884

Published: Aug. 9, 2019

Breast cancer, ranking first among women's cancers worldwide, develops from the breast tissue. Study of tissue is, therefore great significance to diagnosis and treatment cancer. Exosomes, acting as an effective communicator between cells, are in ascendant recent years. One most important cargoes contained exosomes is microRNAs, belonging non-coding RNA family. When exosomal microRNAs absorbed into intracellular location, will act tumor promoters or suppressors by inhibiting translation process target mRNA, thus affecting behavior other stromal cells microenvironment. At present, growing research focuses on different types donor cell sources, their contribution miRNA profiling, biomarker potential, etc. This review aims state function diverse miRNAs medicated cell-cell communication potency some specific enriched molecular markers clinical trials. We also describe mechanism anti-cancer compounds through exploration artificially engineered techniques that lead miRNA-inhibitors for therapeutic use.

Language: Английский

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