MiRNAs as Anti-Angiogenic Adjuvant Therapy in Cancer: Synopsis and Potential

Lahooti, Behnaz; Poudel, Sagun; Mikelis, Constantinos M.; Mattheolabakis, George

doi:10.3389/fonc.2021.705634

Cited by 12 publications

(6 citation statements)

References 156 publications

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“…miR-221 promotes angiogenesis by repressing Cdkn1b and Pik3r1 which are important for tip cell migration [ 272 ]. There is now a growing list of anti-angiogenic and pro-angiogenic miRNAs that operate through different mechanisms and in different pathological settings including cancer and ocular diseases (reviewed in [ 302 ]). Vascular-directed delivery of miRNAs via vascular-homing peptides or nanoparticles may thus be highly effective at targeting angiogenesis in a variety of pathological settings.…”

Section: New Concepts In the Field Of Angiogenesismentioning

confidence: 99%

Pathological angiogenesis: mechanisms and therapeutic strategies

Dudley

2023

Angiogenesis

153

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In multicellular organisms, angiogenesis, the formation of new blood vessels from pre-existing ones, is an essential process for growth and development. Different mechanisms such as vasculogenesis, sprouting, intussusceptive, and coalescent angiogenesis, as well as vessel co-option, vasculogenic mimicry and lymphangiogenesis, underlie the formation of new vasculature. In many pathological conditions, such as cancer, atherosclerosis, arthritis, psoriasis, endometriosis, obesity and SARS-CoV-2(COVID-19), developmental angiogenic processes are recapitulated, but are often done so without the normal feedback mechanisms that regulate the ordinary spatial and temporal patterns of blood vessel formation. Thus, pathological angiogenesis presents new challenges yet new opportunities for the design of vascular-directed therapies. Here, we provide an overview of recent insights into blood vessel development and highlight novel therapeutic strategies that promote or inhibit the process of angiogenesis to stabilize, reverse, or even halt disease progression. In our review, we will also explore several additional aspects (the angiogenic switch, hypoxia, angiocrine signals, endothelial plasticity, vessel normalization, and endothelial cell anergy) that operate in parallel to canonical angiogenesis mechanisms and speculate how these processes may also be targeted with anti-angiogenic or vascular-directed therapies.

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Section: New Concepts In the Field Of Angiogenesismentioning

confidence: 99%

Pathological angiogenesis: mechanisms and therapeutic strategies

Dudley

2023

Angiogenesis

153

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“…More specifically, miR‐21 and its precursor pre‐miR‐21 (Figure 1a) have been in the spotlight after its consistent overexpression has recently been reported in a study profiling 540 clinical samples from cancer patients [8] . The inhibition of miR‐21 function thus holds the promise for both efficient therapy alone, [9a–f] and as an adjuvant to the existing treatments [10a–e] . The search for small molecule inhibitors of miR‐21 is mainly based on the targeting of one of its precursors (pri‐ or pre‐miRNA) that bear secondary structures formed by the presence of single‐stranded regions (loop and bulges) that together with double‐stranded ones induce the formation of specific RNA binding pockets (Figure 1a).…”

Section: Introductionmentioning

confidence: 93%

De‐Novo Design of pre‐miR‐21 Maturation Inhibitors: Synthesis and Activity Assessment

Shcheholeva

Fernández-Remacha

Estrada‐Tejedor

et al. 2023

Chemistry A European J

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Targeting RNA with small molecules is a major challenge of current medicinal chemistry, and the identification and design of original scaffolds able to selectively interact with an RNA target remains difficult. Various approaches have been developed based on classical medicinal chemistry strategies (fragment-based drug design, dynamic combinatorial chemistry, HTS or DNA-encoded libraries) as well as on advanced structural biology and biochemistry methodologies (such as X-ray, cryo-EM, NMR, or SHAPE). Here, we report the de novo design, synthesis, and biological evaluation of RNA ligands by using a straightforward and sustainable chemistry combined with molecular docking and biochemical and biophysical studies that allowed us to identify a novel pharmacophore for RNA binding. Specifically, we focused on targeting the biogenesis of microRNA-21, the well-known oncogene. This led us not only to promising inhibitors but also to a better understanding of the interactions between the small-molecule compounds and the RNA target paving the way for the rational design of efficient inhibitors with potential anticancer activity.

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“…MicroRNAs (miRNAs) are a class of small endogenous noncoding RNAs that regulate the expression of protein-coding genes at the level of transcription and exert biological functions by degrading or inhibiting mRNA expression [1,2]. Studies have reported that miRNAs are widely involved in the biological behavior of cells and disease development, and their abnormal expression is closely related to tumor progression [3,4]. These miR-NAs can be used in the development of anti-cancer drugs and cancer biomarkers [5].…”

Section: Abstract Mir-138-5p Cd44 Breast Cancer Invasion Prognosismentioning

confidence: 99%

Negative regulation of CD44st by miR-138-5p affects the invasive ability of breast cancer cells and patient prognosis after breast cancer surgery

Jian

Bao²,

Li³

et al. 2023

BMC Cancer

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Objective To investigate how the negative regulation of CD44st by miR-138-5p affects the invasive ability of breast cancer cell lines and prognosis in postoperative breast cancer patients. Methods RT-PCR, qRT-PCR, and western blot assays were used to detect the expression of CD44s, CD44v6, and CD44st at both mRNA and protein levels. The expression of miR-138-5p in breast cancer cell lines was also evaluated. The binding ability of miR-138-5p to CD44st was determined via a dual-luciferase assay. The CD44 protein expression in breast cancer tissues was detected using immunohistochemistry. A Transwell assay was used to detect the invasive ability of tumor cells. The correlation between CD44st and miR-138-5p mRNA expression in breast cancer tissues was evaluated using qRT-PCR, and the relationship between clinicopathological features was statistically analyzed. Results CD44s and CD44v6 were highly expressed in MDAMB-231 cell line, while CD44st was highly expressed in MCF-7/Adr and Skbr-3 cells. None of the CD44 isoforms were expressed in MCF-7 cells. The miR-138-5p was highly expressed in MCF-7 cells, but not in MCF-7/Adr, Skbr-3, and MDAMB-231 cells. The dual-luciferase assay suggested that miR-138-5p could bind to wild-type CD44st 3'-UTR, miR-138-5p overexpression significantly inhibited the expression level of CD44 protein in MCF-7/Adr cells, and miR-138-5p + CD44st (3'-UTR)-treated MCF-7/Adr and Skbr-3 cells were significantly less invasive than those in the control group (P < 0.05). RT-PCR results for 80 postoperative breast cancer patients showed that the mRNA expression rate for CD44st was higher in cancer tissues than in paracancerous tissues, and the expression rate of miR-138-5p was higher in paracancerous tissues than in cancerous tissues (P < 0.01). In cancer tissues, CD44st was negatively correlated with miR-138-5p expression, with correlation coefficient r = -0.76 (Pearson’s correlation), coefficient of determination R2 = 0.573, F = 106.89, and P < 0.001. The median overall survival value for patients in the low miR-138-5p expression group was 40.39 months [95% confidence interval (CI): 35.59–45.18 months] and 56.30 months (95% CI: 54.38–58.21 months) for patients in the high-expression group, with a log rank (Mantel-Cox) of 13.120, one degree of freedom, and P < 0.001. Conclusion In breast cancer cell lines, miR-138-5p negatively regulated expression of CD44st and affected the invasive ability of tumor cells and patient prognosis after breast cancer surgery.

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MiRNAs as Anti-Angiogenic Adjuvant Therapy in Cancer: Synopsis and Potential

Cited by 12 publications

References 156 publications

Pathological angiogenesis: mechanisms and therapeutic strategies

Pathological angiogenesis: mechanisms and therapeutic strategies

De‐Novo Design of pre‐miR‐21 Maturation Inhibitors: Synthesis and Activity Assessment

Negative regulation of CD44st by miR-138-5p affects the invasive ability of breast cancer cells and patient prognosis after breast cancer surgery

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