Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Int J Med Sci. 2020 Sep 21;17(17):2635-2643. doi: 10.7150/ijms.50097. eCollection 2020.
Histone deacetylase 6 (HDAC6) controls many cellular processes via its catalyzing deacetylation of downstream substrates or interacting with its partner proteins. Dysregulation of HDAC6 signaling links to many diseases. Our previous study has been reported peptidyl-prolyl cis/trans isomerase, and NIMA-interacting 1 (Pin1) involving in HDAC6-mediated cell motility. To gain insight into precisely coordination of HDAC6 and Pin1 in cell migration, shRNA-mediated gene silencing and ectopic expression were applied to manipulate protein expression level to evaluate relationship between HDAC6 and Pin1 expression. Quantitative RT-PCR and the cycloheximide (CHX) chase assay resulted in HDAC6 expression is correlated with Pin1 level in H1299 cells. It hints that the Pin1 increases HDAC6 expression through increased transcripts and posttranslational stabilization. Furthermore, wound healing assay and transwell invasion assay evidenced the contribution of Pin1 on cell motility in H1299 cells. Our data suggest that Pin1 acts as an important regulator to manage HDAC6 expression for cell motility in lung cancer cells.
组蛋白去乙酰化酶 6（HDAC6）通过其对下游底物的催化去乙酰化作用或与伴侣蛋白相互作用来控制许多细胞过程。HDAC6 信号通路的失调与许多疾病有关。我们之前的研究已经报道了肽基脯氨酰顺/反异构酶（Pin1）参与了 HDAC6 介导的细胞运动。为了深入了解 HDAC6 和 Pin1 在细胞迁移中的精确协调，我们应用 shRNA 介导的基因沉默和异位表达来操纵蛋白质表达水平，以评估 HDAC6 和 Pin1 表达之间的关系。定量 RT-PCR 和环己酰亚胺（CHX）追踪实验表明，在 H1299 细胞中，HDAC6 的表达与 Pin1 水平相关。这表明 Pin1 通过增加转录物和翻译后稳定来增加 HDAC6 的表达。此外，划痕愈合实验和 Transwell 侵袭实验证明了 Pin1 对 H1299 细胞运动的贡献。我们的数据表明，Pin1 作为一个重要的调节剂，通过调节 HDAC6 的表达来控制肺癌细胞的运动能力。
