MITF-M介导的基因调控
中文名称
通路描述
在黑色素瘤细胞中，MITF-M被鉴定为调节涉及细胞外基质（ECM）组织、细胞粘附（FA）和上皮 - 间质转化（EMT）的靶标的调节因子（Dilshat等人，2021）。在SKMel28黑色素瘤细胞系中，siRNA介导的MITF-M敲低导致形态和细胞骨架变化，并促进在基质凝胶上的聚集，表明MITF-M在ECM组织和EMT中的作用。CUT-and-RUN分析鉴定出101个与ECM和FA组织相关的基因，这些基因直接由MITF-M结合，并且在siRNA MITF敲低后表达增加（Dilshat等人，2021），表明MITF-M在这些靶标中起抑制作用。在这些基因中，42个基因在两个独立的黑色素瘤细胞系研究中通过ChIP-seq被鉴定为直接MITF-M靶标（Laurette等人，2015；Webster等人，2014）。MITF-M的表达水平与不同的细胞表型相关，高水平对应增殖表型，低水平对应静止/侵袭表型，EMT和药物耐药性（综述于Rambow等人，2019）。与MITF-M在表型改变中的作用一致，EMT相关基因如CDH1（E - cadherin）、CDH2（N - cadherin）、SOX2和ZEB1也被鉴定为直接MITF-M靶标（Dilshat等人，2021）。
英文描述
Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition Studies in melanoma cells have identified MITF-M as a regulator of targets involved in extracellular matrix organization (ECM), focal adhesion (FA) and epithelial-to-mesenchymal transition (EMT) (Dilshat et al, 2021). siRNA-mediated knockdown of MITF-M in the SKMel28 melanoma cell line causes morphological and cytoskeletal changes and promotes formation of aggregates on matrigel, consistent with a role for MITF-M in ECM organization and EMT. CUT-and-RUN analysis identified 101 genes associated with ECM and FA organization that are directly bound by MITF-M and that show increased expression upon siRNA MITF-knockdown (Dilshat et al, 2021), implicating MITF-M as a repressor of these targets in melanoma cells. Of these, 42 were additionally identified as direct MITF-M targets by ChIP-seq in two independent melanoma cell line studies (Laurette et al, 2015; Webster et al, 2014). MITF-M expression levels are correlated with different cellular phenotypes, with high levels corresponding to a more proliferative phenotype and low levels to a quiescent/invasive phenotype, EMT and drug resistance (reviewed in Rambow et al, 2019). Consistent with a role for MITF-M in phenotypic change, EMT-related genes such as CDH1 (E-cadherin), CDH2 (N-cadherin), SOX2 and ZEB1 were also identified as direct MITF-M targets (Dilshat et al, 2021).
所含基因
12 个基因