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与突变状态和生存相关的黑色素瘤 microRNA 表达谱。

MicroRNA expression profiles associated with mutational status and survival in malignant melanoma.

机构信息

Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

出版信息

J Invest Dermatol. 2010 Aug;130(8):2062-70. doi: 10.1038/jid.2010.63. Epub 2010 Apr 1.


DOI:10.1038/jid.2010.63
PMID:20357817
Abstract

Malignant cutaneous melanoma is a highly aggressive form of skin cancer. Despite improvements in early melanoma diagnosis, the 5-year survival rate remains low in advanced disease. Therefore, novel biomarkers are urgently needed to devise new means of detection and treatment. In this study, we aimed to improve our understanding of microRNA (miRNA) deregulation in melanoma development and their impact on patient survival. Global miRNA expression profiles of a set of melanoma lymph node metastases, melanoma cell lines, and melanocyte cultures were determined using Agilent array. Deregulated miRNAs were evaluated in relation with clinical characteristics, patient survival, and mutational status for BRAF and NRAS. Several miRNAs were differentially expressed between melanocytes and melanomas as well as melanoma cell lines. In melanomas, miR-193a, miR-338, and miR-565 were underexpressed in cases with a BRAF mutation. Furthermore, low expression of miR-191 and high expression of miR-193b were associated with poor melanoma-specific survival. In conclusion, our findings show miRNA dysregulation in malignant melanoma and its relation to established molecular backgrounds of BRAF and NRAS oncogenic mutations. The identification of an miRNA classifier for poor survival may lead to the development of miRNA detection as a complementary prognostic tool in clinical practice.

摘要

恶性皮肤黑色素瘤是一种高度侵袭性的皮肤癌。尽管早期黑色素瘤的诊断有所改善,但晚期疾病的 5 年生存率仍然较低。因此,迫切需要新的生物标志物来设计新的检测和治疗方法。在这项研究中,我们旨在提高对黑色素瘤发展过程中 miRNA 失调及其对患者生存影响的认识。使用 Agilent 阵列测定了一组黑色素瘤淋巴结转移、黑色素瘤细胞系和黑素细胞培养物的全局 miRNA 表达谱。评估了失调 miRNA 与临床特征、患者生存和 BRAF 和 NRAS 突变状态的关系。黑素细胞和黑色素瘤以及黑色素瘤细胞系之间存在几种 miRNA 的差异表达。在黑色素瘤中,miR-193a、miR-338 和 miR-565 在 BRAF 突变病例中表达下调。此外,miR-191 表达降低和 miR-193b 表达升高与黑色素瘤特异性生存不良相关。总之,我们的研究结果表明恶性黑色素瘤存在 miRNA 失调,并且与 BRAF 和 NRAS 致癌突变的既定分子背景有关。识别用于不良生存的 miRNA 分类器可能会导致 miRNA 检测作为临床实践中补充预后工具的发展。

相似文献

[1]
MicroRNA expression profiles associated with mutational status and survival in malignant melanoma.

J Invest Dermatol. 2010-4-1

[2]
MicroRNA and mRNA expression profiling in metastatic melanoma reveal associations with BRAF mutation and patient prognosis.

Pigment Cell Melanoma Res. 2015-5

[3]
Comparative microarray analysis of microRNA expression profiles in primary cutaneous malignant melanoma, cutaneous malignant melanoma metastases, and benign melanocytic nevi.

Cell Tissue Res. 2012-10-31

[4]
Conjunctival malignant melanoma in Denmark: epidemiology, treatment and prognosis with special emphasis on tumorigenesis and genetic profile.

Acta Ophthalmol. 2016-5

[5]
BRAF and NRAS mutations are frequent in nodular melanoma but are not associated with tumor cell proliferation or patient survival.

J Invest Dermatol. 2005-8

[6]
Assessment of clinical parameters associated with mutational status in metastatic malignant melanoma: a single-centre investigation of 141 patients.

Br J Dermatol. 2013-4

[7]
Lymph node metastases of melanoma: challenges for BRAF mutation detection.

Hum Pathol. 2015-1

[8]
A novel oncogenic role for the miRNA-506-514 cluster in initiating melanocyte transformation and promoting melanoma growth.

Oncogene. 2011-8-22

[9]
NRAS and BRAF mutations in melanoma tumours in relation to clinical characteristics: a study based on mutation screening by pyrosequencing.

Melanoma Res. 2006-12

[10]
Marked genetic differences between BRAF and NRAS mutated primary melanomas as revealed by array comparative genomic hybridization.

Melanoma Res. 2012-6

引用本文的文献

[1]
Non-coding RNAs in BRAF-mutant melanoma: targets, indicators, and therapeutic potential.

Naunyn Schmiedebergs Arch Pharmacol. 2025-1

[2]
miR-146a-5p Promotes Angiogenesis and Confers Trastuzumab Resistance in HER2+ Breast Cancer.

Cancers (Basel). 2023-4-4

[3]
Modulating epigenetic modifications for cancer therapy (Review).

Oncol Rep. 2023-3

[4]
Keloid Patient Plasma-Derived Exosomal hsa_circ_0020792 Promotes Normal Skin Fibroblasts Proliferation, Migration, and Fibrogenesis via Modulating miR-193a-5p and Activating TGF-β1/Smad2/3 Signaling.

Drug Des Devel Ther. 2022

[5]
miR2Trait: an integrated resource for investigating miRNA-disease associations.

PeerJ. 2022

[6]
microRNA-193a-5p Suppresses the Migratory Ability of Human KATO III Gastric Cancer Cells through Inhibition of Vimentin and MMP-9.

Adv Pharm Bull. 2022-1

[7]
Integrative analysis of TCGA data identifies miRNAs as drug-specific survival biomarkers.

Sci Rep. 2022-4-26

[8]
The Prognostic Value of miR-125b, miR-200c and miR-205 in Primary Cutaneous Malignant Melanoma Is Independent of BRAF Mutational Status.

Cancers (Basel). 2022-3-16

[9]
miR-498 Targets UBE2T to Inhibit the Proliferation of Malignant Melanoma Cells.

Technol Cancer Res Treat. 2022

[10]
Revisiting miRNA Association with Melanoma Recurrence and Metastasis from a Machine Learning Point of View.

Int J Mol Sci. 2022-1-24

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