Jun Zhang1,2, Xian Zhang3, Shasha Yang1, Yanqiu Bao4, Dongyuan Xu5, Lan Liu6. 1. Department of Morphological Experiment Center, Medical College of Yanbian University, Yanji, Jilin, 133000, China. 2. Department of Histology and Embryology, Jilin Medical University, Jilin, Jilin, 132013, China. 3. Department of General Surgery, Affiliated Hospital of Yanbian University, Yanji, Jilin, 133000, China. 4. Department of Pathology, Affiliated Hospital of Yanbian University, Yanji, Jilin, 133000, China. 5. Department of Morphological Experiment Center, Medical College of Yanbian University, Yanji, Jilin, 133000, China. dyxu@ybu.edu.cn. 6. Department of Pathology, Affiliated Hospital of Yanbian University, Yanji, Jilin, 133000, China. lliu@ybu.edu.c.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: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.
Authors: William T Chiu; Rebekah Charney Le; Ira L Blitz; Margaret B Fish; Yi Li; Jacob Biesinger; Xiaohui Xie; Ken W Y Cho Journal: Development Date: 2014-10-30 Impact factor: 6.868
Authors: Sachin Gopalkrishna Pai; Benedito A Carneiro; Jose Mauricio Mota; Ricardo Costa; Caio Abner Leite; Romualdo Barroso-Sousa; Jason Benjamin Kaplan; Young Kwang Chae; Francis Joseph Giles Journal: J Hematol Oncol Date: 2017-05-05 Impact factor: 17.388