Targeting miRNAs and Other Non-Coding RNAs as a Therapeutic Approach: An Update

Bayraktar, Emine; Bayraktar, Recep; Oztatlici, Hulya; López-Berestein, Gabriel; Amero, Paola; Rodríguez-Aguayo, Cristian

doi:10.3390/ncrna9020027

Cited by 27 publications

(17 citation statements)

References 201 publications

(267 reference statements)

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“…Given the findings presented, therapeutic approaches that specifically targeted miR‐145‐5p/PDK1 axis or long non‐coding RNA STX17‐AS1 presented novel prospects in the realm of hypertrophic scar treatment. Potential strategies that may be employed include the utilization of miRNA antagonists or mimics, notion that has garnered attention since the effective implementation of miRNA‐based therapies in preclinical models 24,25 …”

Section: Discussionmentioning

confidence: 99%

Clinical study on the role of LncRNA STX17‐AS1 in wound healing and hypertrophic scar formation

Wang,

Liu,

et al. 2024

International Wound Journal

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Wound healing is a complex process that can lead to hypertrophic scarring (HS) when dysregulated. The role of lncRNAs in this process is increasingly recognized, yet the specific contributions of lncRNA STX17‐AS1 require elucidation. This study investigated the expression of STX17‐AS1, its regulatory effects on miR‐145‐5p, and downstream targets, highlighting its impact on wound repair and HS development. In a cohort of 20 HS patients and 20 matched controls, we assessed the expression of STX17‐AS1, miR‐145‐5p and PDK1 via real‐time PCR and immunohistochemistry. We correlated these expressions with wound characteristics and analysed their regulatory impact on the PI3K/AKT pathway, crucial for cellular proliferation and migration in wound healing. Elevated levels of STX17‐AS1 and miR‐145‐5p in patient samples were correlated with larger wound areas and slower healing rates, suggesting the regulatory imbalance in scar formation. The negative correlation of PDK1 expression with age and its positive association with wound size underscored its relevance in wound repair mechanisms. Functional analysis confirmed the interaction between STX17‐AS1 and miR‐145‐5p and modulation of PDK1, indicating the potential disruption of the PI3K/AKT pathway in the wound healing process. The study identified lncRNA STX17‐AS1 as the significant mediator in wound healing, with aberrations in its pathway correlating with impaired healing and HS. The findings proposed lncRNA STX17‐AS1 and miR‐145‐5p as molecular targets to enhance wound healing and prevent pathological scarring, offering a new avenue for therapeutic advances in wound management and regenerative medicine.

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Section: Discussionmentioning

confidence: 99%

Clinical study on the role of LncRNA STX17‐AS1 in wound healing and hypertrophic scar formation

Wang,

Liu,

et al. 2024

International Wound Journal

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“…34 Human ex-vivo vein graft model, modelling vascular remodeling 35 could also been used to test the therapeutic potential of the miRNA overexpression. While mimic miRNA have been used in therapy settings, 18 other expression and delivery methods, viral or non-viral 17 might be necessary in vein graft settings to allow a targeted delivery to specific cell type or subtypes.…”

Section: Discussionmentioning

confidence: 99%

“…Due to their potent effect in regulating multiple gene expression changes, miRNA based therapeutics approach has been developed in multiple disease contexts, including cardiovascular disease, with multiple ongoing clinical trials. 17,18 These approaches rely on the ability to modulate miRNA abundance using miRNA mimics, inhibitors, or viral vector-mediated overexpression of miRNA loci. To select the best miRNA candidates for therapy in an unbiased way, functional screen has been developed.…”

Section: Introductionmentioning

confidence: 99%

Functional screening identifies novel miRNAs inhibiting Vascular Smooth Muscle Cell proliferation

Rodor,

Klimi,

Braga

et al. 2024

Preprint

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Proliferation of vascular smooth muscle cells (vSMCs) following injury is a crucial contributor to pathological vascular remodelling. MicroRNAs (miRNAs) are powerful gene regulators and attractive therapeutic agents. Here, we aim to systematically identify and characterise miRNAs with therapeutic potential in targeting aberrant vSMC proliferation. We performed a high-throughput in vitro screen using a library of 2042 human miRNA-mimics for their impact on vSMC proliferation and identified seven novel antiproliferative miRNAs i.e miR-323a-3p, miR449b-5p, miR-491-3p, miR-892b, miR-1827, miR-4774-3p, miR-5681b. Overexpression of these seven miRNAs affects proliferation of vSMCs from different vascular beds. Focusing on vein graft failure, a condition in which miRNA-based therapeutics can be applied to the graft ex-vivo, we showed that these miRNAs reduced human saphenous vein SMC (HSVSMC) proliferation without inducing apoptosis or senescence, and five of them also significantly decreased migration. HSVSMC transcriptomic analysis showed that each miRNA overexpression affects a core cell cycle gene network. However, this effect is mediated by distinct miRNA targets. In contrast to HSVSMC, miRNA overexpression in saphenous vein endothelial cells (ECs) led to no decrease or a less pronounced reduction in proliferation for the seven miRNAs. Transcriptomics analysis confirmed a distinct and limited response of ECs to the miRNA overexpression.

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“…Significant efforts are being focused on the development of targeted and immunotherapies that may improve the prognosis of TNBC patients [ 46 ]. One such strategy involves using miRNAs [ 47 ]. Due to the promising results shown by several preclinical studies using miRNAs as therapeutic targets for TNBC [ 48 ], clinical trials are underway to evaluate the effectiveness of clinical translation of miRNA-based therapy into practice for treatment of different cancers, including TNBC [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Pan-inhibition of the three H2S synthesizing enzymes restrains tumor progression and immunosuppression in breast cancer

Dawoud,

Youness,

Nafea

et al. 2024

Cancer Cell Int

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Background Hydrogen sulfide (H2S) is a significant endogenous mediator that has been implicated in the progression of various forms of cancer including breast cancer (BC). Cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) are the three principal mammalian enzymes responsible for H2S production. Overexpression of CBS, CSE and 3MST was found to be associated with poor prognosis of BC patients. Moreover, H2S was linked to an immune-suppressive tumor microenvironment in BC. Recently it was observed that BC cells, in response to single or dual inhibition of H2S synthesizing enzymes, develop an escape mechanism by overexpressing alternative sources of H2S generation. Thus, the aim of this work is to escape the H2S compensatory mechanism by pan repressing the three enzymes using microRNAs (miRNAs) and to investigate their impact on the oncogenic and immunogenic profile of BC cells. Methods BC female patients (n = 25) were recruited. In-silico analysis was used to identify miRNAs targeting CBS, CSE, and 3MST. MDA-MB-231 cells were cultured and transfected using oligonucleotides. Total RNA was extracted using Biazol, reverse transcribed and quantified using qRT-PCR. H2S levels were measured using AzMc assay. BC hallmarks were assessed using trans-well migration, wound healing, MTT, and colony forming assays. Results miR-193a and miR-548c were validated by eight different bioinformatics software to simultaneously target CBS, CSE and 3MST. MiR-193a and miR-548c were significantly downregulated in BC tissues compared to their non-cancerous counterparts. Ectopic expression of miR-193a and miR-548c in MDA-MB-231 TNBC cells resulted in a marked repression of CBS, CSE, and 3MST transcript and protein levels, a significant decrease in H2S levels, reduction in cellular viability, inhibition of migration and colony forming ability, repression of immune-suppressor proteins GAL3 GAL9, and CD155 and upregulation of the immunostimulatory MICA and MICB proteins. Conclusion This study sheds the light onto miR-193a and miR-548c as potential pan-repressors of the H2S synthesizing enzymes. and identifies them as novel tumor suppressor and immunomodulatory miRNAs in TNBC.

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Targeting miRNAs and Other Non-Coding RNAs as a Therapeutic Approach: An Update

Cited by 27 publications

References 201 publications

Clinical study on the role of LncRNA STX17‐AS1 in wound healing and hypertrophic scar formation

Clinical study on the role of LncRNA STX17‐AS1 in wound healing and hypertrophic scar formation

Functional screening identifies novel miRNAs inhibiting Vascular Smooth Muscle Cell proliferation

Pan-inhibition of the three H2S synthesizing enzymes restrains tumor progression and immunosuppression in breast cancer

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