CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
TOPK 通过 HDAC1 调控 NF-KB 通路影响皮肤鳞状细胞癌的自噬
英文原题：TOPK Affects Autophagy of Skin Squamous Cell Carcinoma by Regulating NF-KB Pathway through HDAC1.
查看英文原题
TOPK Affects Autophagy of Skin Squamous Cell Carcinoma by Regulating NF-KB Pathway through HDAC1.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
研究概要
TOPK 通过上调 HDAC1 激活 NF-κB 通路并促进自噬，从而推动 cSCC 的恶性进展。
研究思路结论见上方概要
探讨T-LAK细胞起源蛋白激酶（TOPK）对皮肤鳞状细胞癌（cSCC）自噬的影响及其潜在机制。
收集临床cSCC癌组织与癌旁组织标本；采用免疫组化法检测cSCC组织中TOPK、核因子κB p65（NF-κB p65）、磷酸化核因子κB抑制蛋白α（p-IκBα）、Beclin-1及微管相关蛋白1轻链3（LC3）的表达；采用免疫荧光法检测cSCC组织中NF-κB p65、p-IκBα与TOPK的共表达。对TOPK沉默或过表达后，分别用PDTC和3-MA处理SCL-1和A431细胞。采用RT-qPCR和Western Blot检测TOPK沉默/过表达细胞中组蛋白去乙酰化酶1（HDAC1）的mRNA和蛋白表达。采用Western Blot检测各组细胞中NF-κB p65、p-p65、IκBα、p-IκBα、Beclin-1和LC3的蛋白表达。采用Transwell和划痕愈合实验检测细胞的侵袭和迁移能力。采用TEM观察各组细胞中自噬体的形成。
与癌旁组织相比，TOPK、NF-κB p65、p-IκBα、Beclin-1和LC3在cSCC癌组织中高表达；TOPK与NF-κB p65共表达；cSCC癌组织中TOPK和p-IκBα的表达均升高。人cSCC细胞中TOPK的mRNA和蛋白水平显著高于人正常皮肤HaCaT细胞。TOPK敲除后，HDAC1、p-IκBα/IκBα、NF-κB p65、p-p65、Beclin-1、LC3II/I蛋白表达、细胞侵袭和迁移能力显著降低，且观察到的自噬体减少。PDTC和3-MA处理显著下调NF-κB通路蛋白活性和自噬水平，并降低细胞迁移和侵袭能力。
展开英文摘要原文
To explore the effect and potential mechanism of T-LAK cell-originated protein kinase (TOPK) on autophagy in cutaneous squamous cell carcinoma (cSCC).
Human cSCC cancer tissue and paracancerous tissue samples were collected clinically; immunohistochemistry was used to detect the expression of TOPK, nuclear factor κ B p65 (NF- κ B p65), phosphorylated nuclear factor κ B inhibitor α (p-I κ B α ), Beclin-1, and microtubule-associated protein 1 light chain 3 (LC3) in cSCC tissue; and immunofluorescence was adopted to detect the coexpression of NF- κ B p65, p-I κ B α , and TOPK in cSCC tissue. After TOPK silencing or overexpression, SCL-1 and A431 cells were treated with PDTC and 3-MA, respectively. RT-qPCR and Western Blot were used to detect the mRNA and protein expressions of histone deacetylase 1 (HDAC1) in TOPK-silenced/overexpressing cells. Western Blot was performed to detect the protein expressions of NF- κ B p65, p-p65, I κ B α , p-I κ B α , Beclin-1, and LC3 in each group. Transwell and scratch healing experiments were used to detect the ability of cells to invade and migrate. The formation of autophagosomes in each group was observed by TEM.
Compared with adjacent tissues, TOPK, NF- κ B p65, p-I κ B α , Beclin-1, and LC3 were highly expressed in cSCC cancer tissues; TOPK and NF- κ B p65 were coexpressed; and TOPK and p-I κ B α were expressed in cSCC cancer tissues both increased. The mRNA and protein levels of TOPK in human cSCC cells were significantly higher than those in human normal skin HaCaT cells. After TOPK knockout, the expression of HDAC1, p-I κ B α /I κ B α , NF- κ B p65, p-p65, Beclin-1, LC3II/I proteins, cell invasion, and migration abilities were significantly reduced, and fewer autophagosomes were observed. Treatment with PDTC and 3-MA significantly downregulated NF- κ B pathway protein activity and autophagy level and reduced cell migration and invasion ability.
TOPK promotes the malignant progression of cSCC by upregulating HDAC1 to activate the NF- κ B pathway and promote autophagy.
论文信息
- 作者
- Li J、Zhang ZC、Yuan XS、Tang SS、Wang T、Liu HF、Cao Y
- 第一作者单位
- Medical College of Soochow University, Suzhou 215123, China.China
- 通讯作者单位
- Clinical Medical College, Guizhou Medical University, Guiyang 550004, China.China
- 期刊
- Disease markers2022
- 原文标识
- PubMed 35756488 · DOI 10.1155/2022/3771711
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →