The miRNAs Role in Melanoma and in Its Resistance to Therapy

Varrone, Francesca; Caputo, Emilia

doi:10.3390/ijms21030878

Cited by 69 publications

(47 citation statements)

References 237 publications

(199 reference statements)

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“…25,26 Interestingly, accumulating studies demonstrated the enrollment of miRNAs in the oncogenesis and progression of melanoma. [27][28][29] MiRNAs may perform tumor-suppressing or tumor-promoting activities in melanoma, and are implicated in the regulation of multiple aggressive processes. 30,31 Hence, studying the expression and roles of miRNAs in melanoma my highlight potential targets for managing melanoma.…”

Section: Introductionmentioning

confidence: 99%

Long Noncoding RNA LINC00173 Promotes the Malignancy of Melanoma by Promoting the Expression of IRS4 Through Competitive Binding to microRNA-493

Yang¹,

Lei²,

Zeng³

et al. 2020

CMAR

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Purpose: Long intergenic non-protein-coding RNA 173 (LINC00173) plays crucial roles in lung cancer. However, the expression and biological functions of LINC00173 in melanoma have not yet been investigated. In this study, we aimed to characterize the involvement of LINC00173 in melanoma and elucidate its mechanisms of action. Materials and Methods: Reverse-transcription quantitative PCR was performed to measure LINC00173 expression in melanoma. A CCK-8 assay, flow cytometry, and migration and invasion assays were applied to examine melanoma cell proliferation, apoptosis, migration, and invasion, respectively. A xenograft tumor experiment was performed to determine the tumorous growth of melanoma cells in vivo. Results: We found that LINC00173 was upregulated in melanoma tissues and cell lines. High LINC00173 expression was closely associated with TNM stage, lymph node metastasis, and shorter overall survival of patients with melanoma. Functional assays revealed that LINC00173 downregulation inhibited melanoma cell proliferation, migration, and invasion and induced apoptosis, suggesting that LINC00173 acts as an oncogenic RNA. LINC00173 knockdown retarded the tumorous growth of melanoma cells in vivo. Mechanistically, LINC00173 increased insulin receptor substrate 4 (IRS4) expression by sponging microRNA-493 (miR-493), thereby acting as a competing endogenous RNA. The effects of LINC00173 knockdown on the malignant phenotype of melanoma cells were reversed by overexpression of IRS4 or knockdown of miR-493. Conclusion: The LINC00173-miR-493-IRS4 pathway regulates melanoma characteristics by increasing the expression of IRS4 via competitive binding of LINC00173 to miR-493, suggesting that this pathway is a potential target for the diagnosis, prognosis, and/or treatment of melanoma.

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Section: Introductionmentioning

confidence: 99%

Long Noncoding RNA LINC00173 Promotes the Malignancy of Melanoma by Promoting the Expression of IRS4 Through Competitive Binding to microRNA-493

Yang¹,

Lei²,

Zeng³

et al. 2020

CMAR

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“…Thus, it is also important to determine whether elevated miRs regulate MAPK pathway. In a previous study, high levels of miR-125b-5p were shown to be associated with Vemurafenib (BRAF inhibitor) resistance [ 47 , 48 ]. Accordingly, we observed that miR-125b was elevated in CII non-responder patients, but decreased in responding patients to CII ( Table S1 ).…”

Section: Discussionmentioning

confidence: 99%

A Pilot Study Comparing the Efficacy of Lactate Dehydrogenase Levels Versus Circulating Cell-Free microRNAs in Monitoring Responses to Checkpoint Inhibitor Immunotherapy in Metastatic Melanoma Patients

Bustos

Gross

Rahimzadeh

et al. 2020

Cancers

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Serum lactate dehydrogenase (LDH) is a standard prognostic biomarker for stage IV melanoma patients. Often, LDH levels do not provide real-time information about the metastatic melanoma patients’ disease status and treatment response. Therefore, there is a need to find reliable blood biomarkers for improved monitoring of metastatic melanoma patients who are undergoing checkpoint inhibitor immunotherapy (CII). The objective in this prospective pilot study was to discover circulating cell-free microRNA (cfmiR) signatures in the plasma that could assess melanoma patients’ responses during CII. The cfmiRs were evaluated by the next-generation sequencing (NGS) HTG EdgeSeq microRNA (miR) Whole Transcriptome Assay (WTA; 2083 miRs) in 158 plasma samples obtained before and during the course of CII from 47 AJCC stage III/IV melanoma patients’ and 73 normal donors’ plasma samples. Initially, cfmiR profiles for pre- and post-treatment plasma samples of stage IV non-responder melanoma patients were compared to normal donors’ plasma samples. Using machine learning, we identified a 9 cfmiR signature that was associated with stage IV melanoma patients being non-responsive to CII. These cfmiRs were compared in pre- and post-treatment plasma samples from stage IV melanoma patients that showed good responses. Circulating miR-4649-3p, miR-615-3p, and miR-1234-3p demonstrated potential prognostic utility in assessing CII responses. Compared to LDH levels during CII, circulating miR-615-3p levels were consistently more efficient in detecting melanoma patients undergoing CII who developed progressive disease. By combining stage III/IV patients, 92 and 17 differentially expressed cfmiRs were identified in pre-treatment plasma samples from responder and non-responder patients, respectively. In conclusion, this pilot study demonstrated cfmiRs that identified treatment responses and could allow for real-time monitoring of patients receiving CII.

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“…The role of miRNAs in melanoma progression is very tangled, therefore excellent reviews can be consulted here: [ 28 , 35 , 36 , 37 ]. In principle, miRNAs influence the evolution of melanoma to secondary sites mainly by: (A) regulating the expression of MITF-M , an essential melanocyte-and melanoma-specific transcription factor that operates as a “switch” in the establishment of an invasive or proliferative phenotype; (B) remodelling the extracellular matrix (ECM); (C) promoting epithelial-to-mesenchymal transition (EMT) and its reverse, mesenchymal-to-epithelial transition (MET); and (D) preparing the formation of the pre-metastatic niche [ 28 , 36 , 38 , 39 , 40 ] ( Figure 1 ).…”

Section: Micrornas Modulate Melanoma Invasion and Metastasismentioning

confidence: 99%

“…The same issue arises with the use of immunotherapy [ 27 ]. The role of ncRNAs in the development of melanoma drug resistance has been questioned and while the contribution of miRNAs is well studied [ 37 ], the role of lncRNAs in such resistance is still largely unknown.…”

Section: Non-coding Rnas In Drug Resistancementioning

confidence: 99%

The Non-Coding Landscape of Cutaneous Malignant Melanoma: A Possible Route to Efficient Targeted Therapy

Lazăr

Dinescu

Costache

2020

Cancers

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Considered to be highly lethal if not diagnosed in early stages, cutaneous malignant melanoma is among the most aggressive and treatment-resistant human cancers, and its incidence continues to rise, largely due to ultraviolet radiation exposure, which is the main carcinogenic factor. Over the years, researchers have started to unveil the molecular mechanisms by which malignant melanoma can be triggered and sustained, in order to establish specific, reliable biomarkers that could aid the prognosis and diagnosis of this fatal disease, and serve as targets for development of novel efficient therapies. The high mutational burden and heterogeneous nature of melanoma shifted the main focus from the genetic landscape to epigenetic and epitranscriptomic modifications, aiming at elucidating the role of non-coding RNA molecules in the fine tuning of melanoma progression. Here we review the contribution of microRNAs and lncRNAs to melanoma invasion, metastasis and acquired drug resistance, highlighting their potential for clinical applications as biomarkers and therapeutic targets.

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The miRNAs Role in Melanoma and in Its Resistance to Therapy

Cited by 69 publications

References 237 publications

<p>Long Noncoding RNA <em>LINC00173</em> Promotes the Malignancy of Melanoma by Promoting the Expression of IRS4 Through Competitive Binding to microRNA-493</p>

<p>Long Noncoding RNA <em>LINC00173</em> Promotes the Malignancy of Melanoma by Promoting the Expression of IRS4 Through Competitive Binding to microRNA-493</p>

A Pilot Study Comparing the Efficacy of Lactate Dehydrogenase Levels Versus Circulating Cell-Free microRNAs in Monitoring Responses to Checkpoint Inhibitor Immunotherapy in Metastatic Melanoma Patients

The Non-Coding Landscape of Cutaneous Malignant Melanoma: A Possible Route to Efficient Targeted Therapy

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