MicroRNAs induced in melanoma treated with combination targeted therapy of Temsirolimus and Bevacizumab

Wagenseller, Aubrey G.; Shada, Amber L.; D’Auria, Kevin M.; Murphy, Cheryl F.; Sun, Dandan; Molhoek, Kerrington R.; Papin, Jason A.; Dutta, Anindya; Slingluff, Craig L.

doi:10.1186/1479-5876-11-218

Cited by 22 publications

(27 citation statements)

References 56 publications

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“…We further explored the prognostic value of miR-150–5p , because it is not expressed in melanoma cell lines and short-term cultures (25, 26), but well detected in melanoma tissues measured in this study and others(27, 28), which likely contain mixed cell-type populations. Since miR-150–5p is highly expressed in mature B and T-cells(29, 30), we hypothesized that differences in its expression between primary melanomas of different outcomes may be reflective of tumor infiltrating lymphocytes (TILs), rather than of a tumor-cell intrinsic property.…”

Section: Resultsmentioning

confidence: 99%

A miRNA-Based Signature Detected in Primary Melanoma Tissue Predicts Development of Brain Metastasis

Hanniford

Zhong

Koetz

et al. 2015

Clinical Cancer Research

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Purpose Brain metastasis is the major cause of mortality among melanoma patients. A molecular prognostic test that can reliably stratify patients at initial melanoma diagnosis by risk of developing brain metastasis may inform the clinical management of these patients. Experimental Design We performed a retrospective, cohort-based study analyzing genome-wide and targeted microRNA expression profiling of primary melanoma tumors of three patient cohorts (n= 92, n= 119, n= 45) with extensive clinical follow up. We used Cox regression analysis to establish a microRNA-based signature that improves the ability of the current clinicopathologic staging system to predict the development of brain metastasis. Results Our analyses identified a 4-microRNA (miR-150–5p, miR-15b-5p, miR-16–5p, and miR-374b-3p) prognostic signature that, in combination with stage, distinguished primary melanomas that metastasized to the brain from non-recurrent and non-brain-metastatic primary tumors (training cohort: C-index=81.4%, validation cohort: C-index=67.4%, independent cohort: C-index=76.9%). Corresponding Kaplan-Meier curves of high- vs. low-risk patients displayed a clear separation in brain-metastasis-free and overall survival (training: p<0.001, p<0.001, validation: p=0.033, p=0.007, independent: p=0.021, p=0.022, respectively). Finally, of the microRNA in the prognostic model, we found that the expression of a key lymphocyte miRNA, miR-150–5p, which is less abundant in primary melanomas metastatic to brain, correlated with presence of CD45+ tumor infiltrating lymphocytes. Conclusions A prognostic assay based on the described miRNA expression signature combined with the currently used staging criteria may improve accuracy of primary melanoma patient prognoses and aid clinical management of patients, including selection for adjuvant treatment or clinical trials of adjuvant therapies.

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Section: Resultsmentioning

confidence: 99%

A miRNA-Based Signature Detected in Primary Melanoma Tissue Predicts Development of Brain Metastasis

Hanniford

Zhong

Koetz

et al. 2015

Clinical Cancer Research

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“…Recently, a number of miRNAs have been demonstrated to play key roles in melanoma (4,5). A recent study applied an Illumina next-generation sequencing platform to conduct an in-depth analysis of the miRNA transcriptome in MM with matched normal skin, and demonstrated that miR-203, -204-5p, -205-5p, -211-5p, -23b-3p, -26a-5p and -26b-5p were significantly decreased in MM (6).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-203 inhibits malignant melanoma cell migration by targeting versican

Yang

2014

Experimental and Therapeutic Medicine

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MicroRNA (miR)-203 has been demonstrated to function as a suppressor in tumorigenesis. Recently, miR-203 was reported to play a role in malignant melanoma (MM); however, the detailed function of miR-203 in MM remains unclear. In the present study, the expression of miR-203 was shown to be significantly downregulated in MM tissues when compared with normal adjacent tissues. Based on a bioinformatic prediction, versican was further identified as a novel target of miR-203, and the expression of versican was markedly increased in MM tissues. Inhibition of miR-203 increased the protein expression of versican, while upregulation of miR-203 inhibited the protein expression of versican in MM A375 cells. In addition, the upregulation of versican significantly promoted A375 cell migration; however, upregulation of miR-203 suppressed A375 cell migration. The present study further investigated whether miR-203 was involved in versican-mediated A375 cell migration, and the results indicated that upregulation of miR-203 significantly inhibited A375 cell migration, which was impaired by overexpression of versican. These observations indicated that versican functions as a downstream effector in miR-203-mediated MM cell migration. Therefore, the results demonstrated that miR-203 exhibited an inhibitory effect on MM cell migration via directly targeting versican, thus, may become an effective inhibitor for MM metastasis.

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“…The down-regulation of miR-320a has been observed in the blood of several cancers including colorectal cancer [25], gastric cancer [26], and retinoblastoma [27]. Moreover, miR-320a is up-regulated in melanoma cells after treatment with Bevacizumab or Rapamycin + Bevacizumab [28]. miR-134 has been characterized as a tumor suppressor, acting to regulate proliferation, apoptosis, and invasion and migration, in a wide range of cancer types including melanoma [31,32].…”

Section: Discussionmentioning

confidence: 99%

The Circulating Transcriptome as a Source of Biomarkers for Melanoma

Solé¹,

Tramonti²,

Schamm³

et al. 2018

Preprint

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The circulating transcriptome is a valuable source of cancer biomarkers, which with the exception of miRNAs, remains relatively unexplored. To elucidate which RNAs are present in plasma from melanoma patients and which could be used to distinguish cancer patients of healthy individuals, we used next generation sequencing (NGS) and validation was carried out by qPCR and/or ddPCR. We identified 442 different microRNAs in samples, eleven of which were differentially expressed (P < 0.05). Levels of miR-134-5p and miR-320a-3p were significantly down-regulated (P<0.001) in melanoma samples (n = 96) compared to healthy controls (n = 28). Differentially expressed protein-encoding mRNA, 5´-fragments, were enriched for the angiopoietin, PAK and EIF2 pathways. Levels of ATM1, AMFR, SOS1 and CD109 gene fragments were up-regulated (P < 0.001) in melanoma samples (n=144) compared to healthy controls (n = 41) (AUC = 0.825). Over 40% of mapped reads were YRNAs, a class of non-coding RNAs that to date has been little explored. Expression levels of RNY3P1, RNY4P1 and RNY4P25 were significantly higher in patients with stage 0 disease, than either healthy controls or more advanced stage disease (P < 0.001). In conclusion, we have identified a number of novel RNA biomarkers, which most importantly we validated in multi-centre retrospective and prospective cohorts suggesting potential diagnostic use of these RNA species.

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MicroRNAs induced in melanoma treated with combination targeted therapy of Temsirolimus and Bevacizumab

Cited by 22 publications

References 56 publications

A miRNA-Based Signature Detected in Primary Melanoma Tissue Predicts Development of Brain Metastasis

A miRNA-Based Signature Detected in Primary Melanoma Tissue Predicts Development of Brain Metastasis

MicroRNA-203 inhibits malignant melanoma cell migration by targeting versican

The Circulating Transcriptome as a Source of Biomarkers for Melanoma

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