MicroRNA expression in BRAF-mutated and wild-type metastatic melanoma and its correlation with response duration to BRAF inhibitors

Pinto, Rosamaria; Strippoli, Sabino; Summa, Simona De; Albano, Anna; Azzariti, Amalia; Guida, Gabriella; Popescu, Ondina; Lorusso, Vito; Guida, Michele; Tommasi, Stefania

doi:10.1517/14728222.2015.1065818

Cited by 26 publications

(20 citation statements)

References 40 publications

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“…24 Through regulating gene expression, miRNAs can impact on different pathways associated with sensitivity or resistance to chemotherapeutic drugs in various tumors. [13][14][15][16][17] Several miRNAs, such as miR-106a, 25 miR-508-5p 26 and miRNA-19a/b 27 have been reported to play a role in the development of MDR in GC. However, miRNAs able to modulate the sensitivity to chemotherapy by regulating genes involved in the hypoxia signaling pathways have not yet been fully addressed in GC.…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12] Recently, microRNAs (miRNAs), small non coding RNAs that act as post-transcriptional repressors of gene expression, have been suggested to play essential roles in modulating chemotherapeutic tumor response. [13][14][15][16][17] We selected some miRNAs that recent literature and bioinformatics tools have highlighted to be involved in MDR1, HIF1A and HIPK2 gene modulation. Several studies have suggested the ability of miR-27a to modulate MDR1/P-gp expression [18][19][20] and the association of miR-181a deregulation with the modulation of HIPK2.…”

Section: Introductionmentioning

confidence: 99%

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Role of miR-27a, miR-181a and miR-20b in gastric cancer hypoxia-induced chemoresistance

Danza

Silvestris

Simone

et al. 2016

Cancer Biology & Therapy

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Despite the search for new therapeutic strategies for gastric cancer (GC), there is much evidence of progression due to resistance to chemotherapy. Multidrug resistance (MDR) is the ability of cancer cells to survive after exposure to chemotherapeutic agents. The involvement of miRNAs in the development of MDR has been well described but miRNAs able to modulate the sensitivity to chemotherapy by regulating hypoxia signaling pathways have not yet been fully addressed in GC. Our aim was to analyze miR-20b, miR-27a and miR-181a expression with respect to (epirubicin/oxaliplatin/capecitabine (EOX)) chemotherapy regimen in a set of GC patients, in order to investigate whether miRNAs deregulation may influence GC MDR also via hypoxia signaling modulation. Cancer biopsy were obtained from 21 untreated HER2 negative advanced GC patients, retrospectively analyzed. All patients received a first-line chemotherapy (EOX) regimen. MirWalk database was used to identify miR-27a, miR-181a and miR-20b target genes. The expression of miRNAs and of HIPK2, HIF1A and MDR1 genes were detected by real-time PCR. HIPK2 localization was assessed by immunohistochemistry. Our data showed the down-regulation of miR-20b, miR-27a, miR-181a concomitantly to higher levels of MDR1, HIF1A and HIPK2 genes in GC patients with a progressive disease respect to those with a disease control rate. Moreover, immunohistochemistry assay highlighted a higher cytoplasmic HIPK2 staining, suggesting a different role for it. We showed that aberrant expression of miR-20b, miR27a and miR-181a was associated with chemotherapeutic response in GC through HIF1A, MDR1 and HIPK2 genes modulation, suggesting a possible novel therapeutic strategy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of miR-27a, miR-181a and miR-20b in gastric cancer hypoxia-induced chemoresistance

Danza

Silvestris

Simone

et al. 2016

Cancer Biology & Therapy

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“…The tumors were most commonly epibulbar (27/37), and local invasion to eyelid skin occurred in four cases. The tumors were staged as T1 (27), T2 (6), and T3 (4). Median tumor thickness was 1.2 mm (range, 0.2-8.0 mm); the CM most commonly originated in a primary acquired melanosis with atypia (PAMþ) (30/37), and a third of the CMs (12/37) were BRAF mutated (Table 1).…”

Section: Patient and Tumor Characteristicsmentioning

confidence: 99%

MicroRNA Expression Profile in Conjunctival Melanoma

Larsen

Mikkelsen

Borup

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Conjunctival melanoma (CM) is a rare disease associated with considerable mortality. As opposed to cutaneous melanoma, the epigenetic mechanisms involved in the development of CM and other mucosal melanomas (MMs) are unclear. The purpose of this study was to identify tumor-specific and prognostic microRNA (miRNA) in CM and to compare the miRNA profile with that of MM.METHODS. Using microarray analysis (Affymetrix) we determined the miRNA expression profile in 40 CMs compared with 7 normal conjunctival samples. Changes in miRNA expression were associated with T stage, local recurrence, metastasis, and mortality. Furthermore, the expression of six fresh frozen tissue samples of CM was compared with that of four laryngeal and sinonasal MM.RESULTS. Our analysis revealed 24 upregulated and 1 downregulated miRNA in CM; several of these miRNAs have key functions in the pathogenesis and progression of cutaneous melanoma. Additionally, we identified seven upregulated miRNAs specific for stage-T1 and stage-T2 CM, whose expression was associated with increased tumor thickness (P ¼ 0.007), and two upregulated miRNAs (miR-3687 and miR-3916) associated with an increased risk of local recurrence. No stage T3-specific miRNAs were identified.CONCLUSIONS. We identified differentially expressed and potentially prognostic miRNAs in CM. Furthermore, the miRNA expression pattern of CM resembled that in MM. The identification of these differentially expressed miRNAs provides an entry point for future functional studies of miRNAs as prognostic or therapeutic targets in CM and highlights the resemblance between CM, MM, and cutaneous melanoma.Keywords: conjunctiva, melanoma, microRNA, gene expression C onjunctival melanomas (CMs) account for approximately 5% of ocular melanomas and they have an associated mortality of up to 30%. 1,2 Recently, oncogenic mutations in BRAF, NRAS, and KIT have been identified in CM, emphasizing their close genetic resemblance to cutaneous and mucosal melanomas (MMs), and their difference from uveal melanomas (UMs). [2][3][4][5] Owing to the high mortality rate associated with CM and MM, 2,6 there is a need to further identify molecular pathways that drive development and progression. MicroRNAs (miRNAs) are small noncoding RNA molecules that epigenetically regulate gene expression at the posttranscriptional level by either degradation of or translational blockage of target messenger RNAs.7 Deregulation of miRNAs with oncogenic and tumor-suppressive functions have attracted much attention owing to their high prevalence.8 These small miRNA molecules could be used as prognostic or therapeutic targets. A microarray-based miRNA expression profiling platform was therefore used to compare the expression of miRNAs in archived (formalin-fixed, paraffin-embedded [FFPE]) CM and normal conjunctival samples. The miRNA expression pattern in CM was tested for associations with TNM stage, 9 local recurrence, metastasis, and mortality in order to identify prognostic miRNAs. To determine similarities in miRNA expressi...

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“…In BRAF-mutated patients treated with Vemurafenib, high expression of miR-192 and miR-193b* and low expression of miR-132 has been associated with short time to progression, indicating a poor prognosis [31].…”

Section: Mirnas Acting As Oncogenesmentioning

confidence: 99%

miRNAs as Key Players in the Management of Cutaneous Melanoma

Lorusso

Summa

Pinto

et al. 2020

Cells

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The number of treatment options for melanoma patients has grown in the past few years, leading to considerable improvements in both overall and progression-free survival. Targeted therapies and immune checkpoint inhibitors have opened a new era in the management of melanoma patients. Despite the clinical advances, further research efforts are needed to identify other "druggable" targets and new biomarkers to improve the stratification of melanoma patients who could really benefit from targeted and immunotherapies. To this end, many studies have focused on the role of microRNAs (miRNAs) that are small non-coding RNAs (18-25 nucleotides in length), which post-transcriptionally regulate the expression of their targets. In cancer, they can behave either as oncogenes or oncosuppressive genes and play a central role in many intracellular pathways involved in proliferation and invasion. Given their modulating activity on the transcriptional landscape, their biological role is under investigation to study resistance mechanisms. They are able to mediate the communication between tumor cells and their microenvironment and regulate tumor immunity through direct regulation of the genes involved in immune activation or suppression. To date, a very promising miRNA-based strategy is to use them as prognosis and diagnosis biomarkers both as cell-free miRNAs and extracellular-vesicle miRNAs. However, miRNAs have a complex role since they target different genes in different cellular conditions. Thus, the ultimate aim of studies has been to recapitulate their role in melanoma in biological networks that account for miRNA/gene expression and mutational state. In this review, we will provide an overview of current scientific knowledge regarding the oncogenic or oncosuppressive role of miRNAs in melanoma and their use as biomarkers, with respect to approved therapies for melanoma treatment.

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MicroRNA expression in BRAF-mutated and wild-type metastatic melanoma and its correlation with response duration to BRAF inhibitors

Cited by 26 publications

References 40 publications

Role of miR-27a, miR-181a and miR-20b in gastric cancer hypoxia-induced chemoresistance

Role of miR-27a, miR-181a and miR-20b in gastric cancer hypoxia-induced chemoresistance

MicroRNA Expression Profile in Conjunctival Melanoma

miRNAs as Key Players in the Management of Cutaneous Melanoma

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