Consequences of genetic variants in miRNA genes

Machowska, Magdalena; Galka-Marciniak, Paulina; Kozlowski, Piotr

doi:10.1016/j.csbj.2022.11.036

Cited by 13 publications

(5 citation statements)

References 161 publications

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“…It is relevant to highlight, as mentioned, that the differential miRNA expression among racial and ethnic groups can occur in individuals from the general population [22,25]. These expression differences are, however, mainly attributed to polymorphisms of SNPs that can occur in pre-miRNAs and mature miRNA binding sites and that exhibit varying allele frequencies in different populations [21,73].…”

Section: Discussionmentioning

confidence: 99%

“…MiRNA expression have been shown to vary among different ancestries. Several mechanisms can contribute to this variability, including genetic variations, such as single nucleotide polymorphisms (SNPs) and other genetic changes, that can influence miRNA biogenesis and function, leading to differences in miRNA expression between populations [21][22][23]. In addition, natural selection and environmental factors may contribute to the enrichment or depletion of specific miRNA variants in different ancestries, affecting the miRNA regulation of genes involved in disease pathways [24,25].…”

Section: Introductionmentioning

confidence: 99%

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Deregulated miRNA Expression in Triple-Negative Breast Cancer of Ancestral Genomic-Characterized Latina Patients

Almohaywi,

Sugita,

Centa

et al. 2023

IJMS

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Among patients with triple-negative breast cancer (TNBC), several studies have suggested that deregulated microRNA (miRNA) expression may be associated with a more aggressive phenotype. Although tumor molecular signatures may be race- and/or ethnicity-specific, there is limited information on the molecular profiles in women with TNBC of Hispanic and Latin American ancestry. We simultaneously profiled TNBC biopsies for the genome-wide copy number and miRNA global expression from 28 Latina women and identified a panel of 28 miRNAs associated with copy number alterations (CNAs). Four selected miRNAs (miR-141-3p, miR-150-5p, miR-182-5p, and miR-661) were validated in a subset of tumor and adjacent non-tumor tissue samples, with miR-182-5p being the most discriminatory among tissue groups (AUC value > 0.8). MiR-141-3p up-regulation was associated with increased cancer recurrence; miR-661 down-regulation with larger tumor size; and down-regulation of miR-150-5p with larger tumor size, high p53 expression, increased cancer recurrence, presence of distant metastasis, and deceased status. This study reinforces the importance of integration analysis of CNAs and miRNAs in TNBC, allowing for the identification of interactions among molecular mechanisms. Additionally, this study emphasizes the significance of considering the patients ancestral background when examining TNBC, as it can influence the relationship between intrinsic tumor molecular characteristics and clinical manifestations of the disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Deregulated miRNA Expression in Triple-Negative Breast Cancer of Ancestral Genomic-Characterized Latina Patients

Almohaywi,

Sugita,

Centa

et al. 2023

IJMS

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“…A variation within an miRNA sequence may impact the functionality of the miRNA, if it affects the stability of the MTI. An SNP that lies in a regulatory region and influences the expression level of an miRNA may also affect the expression levels of the miRNA targets [103][104][105]. Importantly, such profound effects may, in turn, contribute to disease, therefore leading to an increased focus in recent years on genetic variants within miRNAs and miRNA-target binding sites.…”

Section: Tools For Snp Effect Predictionmentioning

confidence: 99%

Insights into Online microRNA Bioinformatics Tools

Buitrago

Lovering

Caporali

2023

ncRNA

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MicroRNAs (miRNAs) are members of the small non-coding RNA family regulating gene expression at the post-transcriptional level. MiRNAs have been found to have critical roles in various biological and pathological processes. Research in this field has significantly progressed, with increased recognition of the importance of miRNA regulation. As a result of the vast data and information available regarding miRNAs, numerous online tools have emerged to address various biological questions related to their function and influence across essential cellular processes. This review includes a brief introduction to available resources for an investigation covering aspects such as miRNA sequences, target prediction/validation, miRNAs associated with disease, pathway analysis and genetic variants within miRNAs.

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“…For example, it is widely recognized that various factors such as genetic deletions or amplifications, epigenetic methylation of miRNA genomic loci, and modifications affecting the regulation of primary miRNAs (pri-miRNA) by transcription factors, alongside components involved in the miRNA biogenesis pathway frequently lead to alterations in miRNA expression and function across numerous cancer types [56,78,79].…”

Section: Introductionmentioning

confidence: 99%

Trials and Tribulations of MicroRNA Therapeutics

Seyhan

2024

IJMS

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The discovery of the link between microRNAs (miRNAs) and a myriad of human diseases, particularly various cancer types, has generated significant interest in exploring their potential as a novel class of drugs. This has led to substantial investments in interdisciplinary research fields such as biology, chemistry, and medical science for the development of miRNA-based therapies. Furthermore, the recent global success of SARS-CoV-2 mRNA vaccines against the COVID-19 pandemic has further revitalized interest in RNA-based immunotherapies, including miRNA-based approaches to cancer treatment. Consequently, RNA therapeutics have emerged as highly adaptable and modular options for cancer therapy. Moreover, advancements in RNA chemistry and delivery methods have been pivotal in shaping the landscape of RNA-based immunotherapy, including miRNA-based approaches. Consequently, the biotechnology and pharmaceutical industry has witnessed a resurgence of interest in incorporating RNA-based immunotherapies and miRNA therapeutics into their development programs. Despite substantial progress in preclinical research, the field of miRNA-based therapeutics remains in its early stages, with only a few progressing to clinical development, none reaching phase III clinical trials or being approved by the US Food and Drug Administration (FDA), and several facing termination due to toxicity issues. These setbacks highlight existing challenges that must be addressed for the broad clinical application of miRNA-based therapeutics. Key challenges include establishing miRNA sensitivity, specificity, and selectivity towards their intended targets, mitigating immunogenic reactions and off-target effects, developing enhanced methods for targeted delivery, and determining optimal dosing for therapeutic efficacy while minimizing side effects. Additionally, the limited understanding of the precise functions of miRNAs limits their clinical utilization. Moreover, for miRNAs to be viable for cancer treatment, they must be technically and economically feasible for the widespread adoption of RNA therapies. As a result, a thorough risk evaluation of miRNA therapeutics is crucial to minimize off-target effects, prevent overdosing, and address various other issues. Nevertheless, the therapeutic potential of miRNAs for various diseases is evident, and future investigations are essential to determine their applicability in clinical settings.

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Consequences of genetic variants in miRNA genes

Cited by 13 publications

References 161 publications

Deregulated miRNA Expression in Triple-Negative Breast Cancer of Ancestral Genomic-Characterized Latina Patients

Deregulated miRNA Expression in Triple-Negative Breast Cancer of Ancestral Genomic-Characterized Latina Patients

Insights into Online microRNA Bioinformatics Tools

Trials and Tribulations of MicroRNA Therapeutics

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