Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
Int J Mol Sci. 2019 Jun 19;20(12):2997. doi: 10.3390/ijms20122997.
Actin filaments are a major component of the cytoskeleton in eukaryotic cells and play an important role in cancer metastasis. Dynamics and reorganization of actin filaments are regulated by numerous regulators, including Rho GTPases, PAKs (p21-activated kinases), ROCKs (Rho-associated coiled-coil containing kinases), LIMKs (LIM domain kinases), and SSH1 (slingshot family protein phosphate 1). Ubiquitination, as a ubiquitous post-transcriptional modification, deceases protein levels of actin cytoskeleton regulatory factors and thereby modulates the actin cytoskeleton. There is increasing evidence showing cytoskeleton regulation by long noncoding RNAs (lncRNAs) in cancer metastasis. However, which E3 ligases are activated for the ubiquitination of actin-cytoskeleton regulators involved in tumor metastasis remains to be fully elucidated. Moreover, it is not clear how lncRNAs influence the expression of actin cytoskeleton regulators. Here, we summarize physiological and pathological mechanisms of lncRNAs and ubiquitination control mediators of actin cytoskeleton regulators which that are involved in tumorigenesis and tumor progression. Finally, we briefly discuss crosstalk between ubiquitination and lncRNA control mediators of actin-cytoskeleton regulators in cancer.
肌动蛋白丝是真核细胞细胞骨架的主要成分,在癌症转移中发挥重要作用。肌动蛋白丝的动力学和重组由许多调节剂调节,包括 Rho GTPases、PAKs(p21 激活激酶)、ROCKs(Rho 相关卷曲螺旋激酶)、LIMKs(LIM 结构域激酶)和 SSH1(弹弓家族蛋白磷酸酶 1)。泛素化作为一种普遍的转录后修饰,降低了肌动蛋白细胞骨架调节因子的蛋白水平,从而调节肌动蛋白细胞骨架。越来越多的证据表明,长非编码 RNA(lncRNA)在癌症转移中对细胞骨架的调节作用。然而,哪些 E3 连接酶被激活用于参与肿瘤转移的肌动蛋白细胞骨架调节剂的泛素化仍有待充分阐明。此外,lncRNA 如何影响肌动蛋白细胞骨架调节剂的表达尚不清楚。在这里,我们总结了 lncRNA 和肌动蛋白细胞骨架调节剂的泛素化调控因子在肿瘤发生和肿瘤进展中的生理和病理机制。最后,我们简要讨论了泛素化和 lncRNA 对肌动蛋白细胞骨架调节剂调控因子的相互作用在癌症中的作用。