FOXH1 promotes lung cancer progression by activating the Wnt/β-catenin signaling pathway.
FOXH1 promotes lung cancer progression by activating the Wnt/β-catenin signaling pathway.
复制标题
FOXH1通过激活Wnt/β-catenin信号通路促进肺癌进展
DOI：
10.1186/s12935-021-01995-9
复制
发表时间：
2021-06-05
影响因子：
5.8
通讯作者：
Liu L
中科院分区：
文献类型：
--
作者：
Zhang J;Zhang X;Yang S;Bao Y;Xu D;Liu L
叉头盒蛋白 H1 (FOXH1) 的表达在多种癌症中经常上调。然而，FOXH1 表达与肺癌进展之间关联的分子机制仍然知之甚少。因此，本研究的主要目的是探讨FOXH1在肺癌中的作用。癌症基因组图谱数据集用于研究肺癌组织中的 FOXH1 表达，Kaplan-Meier 绘图仪数据集用于确定 FOXH1 在患者预后中的作用。 A549 和 PC9 细胞用靶向 FOXH1 mRNA 的短发夹 RNA 转染。采用Cell Counting Kit-8、集落形成、软琼脂、伤口愈合、Transwell侵袭和流式细胞术检测来评估肺癌细胞的增殖、迁移和侵袭。在 BALB/c 裸鼠模型中检查致瘤性。进行蛋白质印迹分析以评估分子机制，并通过荧光素酶报告系统测定测量β-连环蛋白活性。在肿瘤组织中观察到 FOXH1 的表达水平高于正常组织，这与较差的总生存率相关。 FOXH1 的敲低显着抑制肺癌细胞的增殖、迁移、侵袭和周期。此外，小鼠异种移植模型表明，FOXH1 的敲除可抑制体内肿瘤生长。进一步的实验表明，FOXH1缺失通过下调间质标志物（Snail、Slug、基质金属蛋白酶-2、N-钙粘蛋白和波形蛋白）的表达并上调上皮标志物（E-钙粘蛋白）的表达来抑制肺癌细胞的上皮-间质转化。此外，敲低 FOXH1 显着下调 β-连环蛋白及其下游靶标 p-GSK-3β 和细胞周期蛋白 D1 的活性。 FOXH1 通过调节 Wnt/β-catenin 信号通路在肺癌中发挥致癌功能。 FOXH1 可能是某些类型肺癌患者的潜在治疗靶点。在线版本包含可在 10.1186/s12935-021-01995-9 获取的补充材料。
The expression of forkhead box protein H1 (FOXH1) is frequently upregulated in various cancers. However, the molecular mechanisms underlying the association between FOXH1 expression and lung cancer progression still remain poorly understood. Thus, the main objective of this study is to explore the role of FOXH1 in lung cancer. The Cancer Genome Atlas dataset was used to investigate FOXH1 expression in lung cancer tissues, and the Kaplan–Meier plotter dataset was used to determine the role of FOXH1 in patient prognosis. A549 and PC9 cells were transfected with short hairpin RNA targeting FOXH1 mRNA. The Cell Counting Kit-8, colony formation, soft agar, wound healing, transwell invasion and flow cytometry assays were performed to evaluate proliferation, migration and invasion of lung cancer cells. Tumorigenicity was examined in a BALB/c nude mice model. Western blot analysis was performed to assess the molecular mechanisms, and β-catenin activity was measured by a luciferase reporter system assay. Higher expression level of FOXH1 was observed in tumor tissue than in normal tissue, and this was associated with poor overall survival. Knockdown of FOXH1 significantly inhibited lung cancer cell proliferation, migration, invasion, and cycle. In addition, the mouse xenograft model showed that knockdown of FOXH1 suppressed tumor growth in vivo. Further experiments revealed that FOXH1 depletion inhibited the epithelial-mesenchymal transition of lung cancer cells by downregulating the expression of mesenchymal markers (Snail, Slug, matrix metalloproteinase-2, N-cadherin, and Vimentin) and upregulating the expression of an epithelial marker (E-cadherin). Moreover, knockdown of FOXH1 significantly downregulated the activity of β-catenin and its downstream targets, p-GSK-3β and cyclin D1. FOXH1 exerts oncogenic functions in lung cancer through regulation of the Wnt/β-catenin signaling pathway. FOXH1 might be a potential therapeutic target for patients with certain types of lung cancer. The online version contains supplementary material available at 10.1186/s12935-021-01995-9.
登录
查看更多内容
影响因子：
4.1
作者：
Attisano, L;Silvestri, C;Labbé, E
通讯作者：
Labbé, E
影响因子：
7.3
作者：
Gonzalez DM;Medici D
通讯作者：
Medici D
影响因子：
4.3
作者：
Li, Li-Fu;Wei, Zheng-Jie;Jiang, Bo
通讯作者：
Jiang, Bo
影响因子：
3.4
作者：
Liu, Yunli;Xu, Yangyang;Chen, Zhaoyan
通讯作者：
Chen, Zhaoyan
影响因子：
7.6
作者：
Scanlon, C. S.;Van Tubergen, E. A.;D'Silva, N. J.
通讯作者：
D'Silva, N. J.