The expression of RUNDC3B is associated with promoter methylation in lymphoid malignancies.
The expression of RUNDC3B is associated with promoter methylation in lymphoid malignancies.
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DOI：
10.1002/hon.2238
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发表时间：
2017-03
影响因子：
3.3
通讯作者：
Taylor KH
中科院分区：
文献类型：
--
作者：
Burmeister DW;Smith EH;Cristel RT;McKay SD;Shi H;Arthur GL;Davis JW;Taylor KH
DNA甲基化是一种表观遗传修饰，在基因表达调控中起着重要作用。RUNDC 3B的功能尚未确定，尽管其表达失调与乳腺癌和肺癌的恶性潜能相关。为了阐明使用RUNDC 3B中的DNA甲基化作为淋巴恶性肿瘤中的生物标志物的潜力，在癌细胞系中测定了跨越RUNDC 3B的启动子区域中的CpG岛的六个区域的甲基化状态。与髓系恶性肿瘤和实体瘤相比，髓系恶性肿瘤具有更显著的甲基化，并且不表达RUNDC3B，这支持了该区域中DNA甲基化作为淋巴恶性肿瘤生物标志物的潜在用途。RUNDC3B在其N末端区域含有一个RUN结构域，介导与Rap2的相互作用，Rap2是丝裂原活化蛋白激酶（MAPK）级联的重要组分，调节细胞增殖和分化。RUNDC 3B的蛋白质序列还含有MAPK中间体的特征性结合位点。因此，RUNDC3B可能是Rap2和MAPK信号级联之间的介导者。在甲基化白血病细胞系（HSPA5、Jun和Fos）中，MAPK诱导表达的三个基因下调。Jun和Fos联合收割机形成活化蛋白1转录因子，该因子的缺失与参与分化和增殖的基因的失调有关。我们推测，RUNDC3B的损失继发于早期生长反应3转录因子结合位点的异常超甲基化，导致MAPK信号转导失调和淋巴恶性肿瘤的癌变。© 2015作者。出版社：John Wiley & Sons Ltd
DNA methylation is an epigenetic modification that plays an important role in the regulation of gene expression. The function of RUNDC3B has yet to be determined, although its dysregulated expression has been associated with malignant potential of both breast and lung carcinoma. To elucidate the potential of using DNA methylation in RUNDC3B as a biomarker in lymphoid malignancies, the methylation status of six regions spanning the CpG island in the promoter region of RUNDC3B was determined in cancer cell lines. Lymphoid malignancies were found to have more prominent methylation and did not express RUNDC3B compared with myeloid malignancies and solid tumours, supporting the potential use of DNA methylation in this region as a biomarker for lymphoid malignancies. RUNDC3B contains a RUN domain in its N‐terminal region that mediates interaction with Rap2, an important component of the mitogen‐activated protein kinase (MAPK) cascade, which regulates cellular proliferation and differentiation. The protein sequence of RUNDC3B also contains characteristic binding sites for MAPK intermediates. Therefore, it is possible that RUNDC3B serves as a mediator between Rap2 and the MAPK signalling cascade. Three genes with MAPK‐inducible expression were downregulated in a methylated leukaemia cell line (HSPA5, Jun and Fos). Jun and Fos combine to form the activating protein 1 transcription factor, and loss of this factor is associated with the dysregulation of genes involved in differentiation and proliferation. We hypothesize that the loss of RUNDC3B secondary to aberrant hypermethylation of the early growth response 3 transcription factor binding site results in dysregulated MAPK signalling and carcinogenesis in lymphoid malignancies. © 2015 The Authors. Hematological Oncology published by John Wiley & Sons Ltd