Effects of RNA methylation N6-methyladenosine regulators on malignant progression and prognosis of melanoma.
Effects of RNA methylation N6-methyladenosine regulators on malignant progression and prognosis of melanoma.
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RNA甲基化N6-甲基腺苷调节剂对黑色素瘤恶性进展和预后的影响。
DOI：
10.1186/s12935-021-02163-9
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发表时间：
2021-08-26
影响因子：
5.8
通讯作者：
Yao G
中科院分区：
文献类型：
--
作者：
Liu J;Zhou Z;Ma L;Li C;Lin Y;Yu T;Wei JF;Zhu L;Yao G
黑色素瘤是一种极具侵袭性的皮肤癌，近年来死亡率迅速上升。迫切需要探索新的潜在预后生物标志物和黑色素瘤的治疗靶点。本研究的目标是鉴定遗传标记并评估n6 -甲基腺苷（m6A）调节因子在黑色素瘤中的预后表现。从The Cancer Genome Atlas （TCGA）和Genotype-Tissue expression （GTEx）数据库中收集黑色素瘤患者的基因表达数据和相应的临床信息，以及正常对照的序列数据。采用实时荧光定量PCR （Quantitative real-time PCR, qRT-PCR）检测IGF2BP3 RNA在A375细胞系、黑色素瘤组织和正常组织中的表达情况。通过Western blot、细胞增殖和迁移实验来评估IGF2BP3在A375细胞系中的能力。分析肿瘤样本与正常样本之间m6A调控因子的表达差异。构建了包括IGF2BP3、RBM15B和METTL16在内的三基因预后标记，并确定该标记的风险评分为黑色素瘤的独立预后指标。此外，IGF2BP3在体外被证实促进黑色素瘤细胞的增殖和迁移，并在临床样本中与淋巴结转移有关。此外，风险评分和IGF2BP3的表达与浸润的免疫细胞呈正相关，这些枢纽基因是黑色素瘤中极好的潜在药物靶点。我们确定了m6A调控基因的遗传变化，并构建了一个在黑色素瘤中具有独特预后价值的三基因风险标记。这项研究为m6A调控因子的表观遗传学理解和黑色素瘤的新治疗策略提供了新的见解。在线版本包含补充材料，可在10.1186/s12935-021-02163-9获得。
Melanoma is an extremely aggressive type of skin cancer and experiencing a expeditiously rising mortality in a current year. Exploring new potential prognostic biomarkers and therapeutic targets of melanoma are urgently needed. The ambition of this research was to identify genetic markers and assess prognostic performance of N6-methyladenosine (m6A) regulators in melanoma. Gene expression data and corresponding clinical informations of melanoma patients as well as sequence data of normal controls are collected from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Quantitative real-time PCR (qRT-PCR) analysis was carried out to detect the RNA expression of IGF2BP3 in A375 cell line, melanoma tissues, and normal tissues. Western blot, cell proliferation, and migration assays were performed to assess the ability of IGF2BP3 in A375 cell line. Differently expressed m6A regulators between tumor samples and normal samples were analyzed. A three-gene prognostic signature including IGF2BP3, RBM15B, and METTL16 was constructed, and the risk score of this signature was identified to be an independent prognostic indicator for melanoma. In addition, IGF2BP3 was verified to promote melanoma cell proliferation and migration in vitro and associate with lymph node metastasis in clinical samples. Moreover, risk score and the expression of IGF2BP3 were positively associated with the infiltrating immune cells and these hub genes made excellent potential drug targets in melanoma. We identified the genetic changes in m6A regulatory genes and constructed a three-gene risk signature with distinct prognostic value in melanoma. This research provided new insights into the epigenetic understanding of m6A regulators and novel therapeutic strategies in melanoma. The online version contains supplementary material available at 10.1186/s12935-021-02163-9.
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影响因子：
4
作者：
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DOI：
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DOI：
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发表时间：
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期刊：
Aging
影响因子：
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