MicroRNA Isoforms Contribution to Melanoma Pathogenesis

Broseghini, Elisabetta; Dika, Emi; Londin, Eric; Ferracin, Manuela

doi:10.3390/ncrna7040063

Cited by 9 publications

(5 citation statements)

References 59 publications

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“…Furthermore, isomiRs may be more informative than miRs as biomarkers for differentiating cancer types 14 , and their relative expression levels differ across sex and population boundaries 27 . An example is the different expression profiles of isomiRs in melanoma samples compared with the reference, canonical form 28 . It also has been established that intracellular levels of isomiRs are differentially regulated upon stimulation (e.g., by type I interferon) 19 .…”

Section: Discussionmentioning

confidence: 99%

Rapid and accurate quantification of isomiRs by RT-qPCR

Franco

Pluvinet

Sánchez-Herrero

et al. 2022

Sci Rep

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Currently, microRNAs (miRs) are annotated as a single defined sequence (canonical), even though high-throughput small RNA sequencing has identified miR isoforms (isomiRs) that differ from their canonical counterparts in length, sequence, or both. Here we describe a simple reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR)-based assay for quantification of the miR-100-5p_iso_3p:−2 variant. We chose miR-100-5p because the canonical sequence was underrepresented in our evaluation of human plasma. The quantification of miR-100-5p_iso_3 p:−2 from 57 plasma samples demonstrated high concordance between high-throughput RNA sequencing and RT-qPCR results (r = 0.55, p < 0.0001). Of note, we could not detect or quantify miR-100-5p in our plasma samples using a commercial TaqMan canonical miR-100-5p RT-qPCR kit. With these 57 samples, we also adapted this assay to specifically quantify the canonical sequences of miR-122-5p and miR-192-5p. Similar to the results obtained with miR-100-5p_iso_3p:−2, RT-qPCR results for miR-122-5p and miR-192-5p highly correlated with high-throughput RNA sequencing data (miR-122-5p: r = 0.44, p = 0.0005; miR-192-5p: r = 0.72, p < 0.0001). The assay described here can be easily adapted to many different identified isomiRs. Because of the high specificity of isomiRs, their reliable RT-qPCR-based quantification could provide greater resolution and higher accuracy than using canonical sequences.

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Section: Discussionmentioning

confidence: 99%

Rapid and accurate quantification of isomiRs by RT-qPCR

Franco

Pluvinet

Sánchez-Herrero

et al. 2022

Sci Rep

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“…In addition to DNA methylation and histone modification, non-coding RNA and m 6 A RNA methylation are also critical types of epigenetic modification. The expression profiles of microRNAs, lncRNAs, and circRNAs in melanoma have been extensively studied and are found to be associated with a variety of tumor hallmarks ( 107 – 110 ). Studies of miRNAs in melanoma initially focused on their roles as potential biomarkers ( 111 ).…”

Section: Epigenetics In Melanoma Antitumor Immunitymentioning

confidence: 99%

Epigenetics Regulates Antitumor Immunity in Melanoma

Chen

Sun

et al. 2022

Front. Immunol.

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Melanoma is the most malignant skin cancer, which originates from epidermal melanocytes, with increasing worldwide incidence. The escape of immune surveillance is a hallmark of the tumor, which is manifested by the imbalance between the enhanced immune evasion of tumor cells and the impaired antitumor capacity of infiltrating immune cells. According to this notion, the invigoration of the exhausted immune cells by immune checkpoint blockades has gained encouraging outcomes in eliminating tumor cells and significantly prolonged the survival of patients, particularly in melanoma. Epigenetics is a pivotal non-genomic modulatory paradigm referring to heritable changes in gene expression without altering genome sequence, including DNA methylation, histone modification, non-coding RNAs, and m6A RNA methylation. Accumulating evidence has demonstrated how the dysregulation of epigenetics regulates multiple biological behaviors of tumor cells and contributes to carcinogenesis and tumor progression in melanoma. Nevertheless, the linkage between epigenetics and antitumor immunity, as well as its implication in melanoma immunotherapy, remains elusive. In this review, we first introduce the epidemiology, clinical characteristics, and therapeutic innovations of melanoma. Then, the tumor microenvironment and the functions of different types of infiltrating immune cells are discussed, with an emphasis on their involvement in antitumor immunity in melanoma. Subsequently, we systemically summarize the linkage between epigenetics and antitumor immunity in melanoma, from the perspective of distinct paradigms of epigenetics. Ultimately, the progression of the clinical trials regarding epigenetics-based melanoma immunotherapy is introduced.

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“…For instance, Giuliani et al (23) found that out of 133 differentially expressed (DE) isomiRs, only half showed DE in their respective reference miRNAs, when analyzed using traditional miRNA methods. Another study identified instances where isomiRs, derived from the same reference sequence, were DE in opposite directions (24). These findings not only cast doubts on the efficacy of standard methods but also emphasize the importance of understanding the role of isomiRs in DE to prevent discrepancies between computational results and biological reality before pursuing experimental validations, which usually focus on targeting or inhibiting specific sequences.…”

Section: Introductionmentioning

confidence: 99%

The critical role of isomiRs in accurate differential expression analysis of miRNA-seq data

Schmauch,

Attia,

Laitinen

et al. 2024

Preprint

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MicroRNAs (miRNAs) are crucial for the regulation of gene expression and are promising biomarkers and therapeutic targets. miRNA isoforms (isomiRs) differ in their start/end offsets, which can impact the target gene selection and non-canonical function of the miRNA species. In addition, isomiRs frequently differ in their expression patterns from their parent miRNAs, yet their roles and tissue-specific responses are currently understudied, leading to their typical omission in miRNA research. Here, we evaluate the expression differences of isomiRs across conditions and their impact on standard miRNA-seq quantification results. We analyze 28 public miRNA-seq datasets, showing significant expression pattern differences between the isomiRs and their corresponding reference miRNAs, leading to misinterpretation of differential expression signals for both. As a case study, we generate a new dataset assessing isomiR abundance under hypoxia in human endothelial cells between the nuclear and cytosolic compartments. The results suggest that isomiRs are dramatically altered in their nuclear localization in response to hypoxia, indicating a potential non-canonical effect of the species, which would be missed without isomiR-aware analysis. Our results call for a comprehensive re-evaluation of the miRNA-seq analysis practices.

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MicroRNA Isoforms Contribution to Melanoma Pathogenesis

Cited by 9 publications

References 59 publications

Rapid and accurate quantification of isomiRs by RT-qPCR

Rapid and accurate quantification of isomiRs by RT-qPCR

Epigenetics Regulates Antitumor Immunity in Melanoma

The critical role of isomiRs in accurate differential expression analysis of miRNA-seq data

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