BackgroundThe 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.MethodsThe 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 beta -catenin activity was measured by a luciferase reporter system assay.ResultsHigher 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 beta -catenin and its downstream targets, p-GSK-3 beta and cyclin D1.ConclusionFOXH1 exerts oncogenic functions in lung cancer through regulation of the Wnt/beta -catenin signaling pathway. FOXH1 might be a potential therapeutic target for patients with certain types of lung cancer.
机构:
Ist Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Dept Med Oncol, Via P Maroncelli 40, I-47014 Meldola, ItalyIst Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Dept Med Oncol, Via P Maroncelli 40, I-47014 Meldola, Italy
Bronte, Giuseppe
Bravaccini, Sara
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Ist Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Biosci Lab, Meldola, ItalyIst Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Dept Med Oncol, Via P Maroncelli 40, I-47014 Meldola, Italy
Bravaccini, Sara
Bronte, Enrico
论文数: 0引用数: 0
h-index: 0
机构:
Univ Palermo, Dept Surg Oncol & Oral Sci, Palermo, ItalyIst Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Dept Med Oncol, Via P Maroncelli 40, I-47014 Meldola, Italy
Bronte, Enrico
Burgio, Marco Angelo
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h-index: 0
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Ist Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Dept Med Oncol, Via P Maroncelli 40, I-47014 Meldola, ItalyIst Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Dept Med Oncol, Via P Maroncelli 40, I-47014 Meldola, Italy
Burgio, Marco Angelo
Rolfo, Christian
论文数: 0引用数: 0
h-index: 0
机构:
Univ Ziekenhuis Antwerpen, Dept Oncol, Phase Early Clin Trials Unit 1, Edegem, BelgiumIst Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Dept Med Oncol, Via P Maroncelli 40, I-47014 Meldola, Italy
Rolfo, Christian
Delmonte, Angelo
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h-index: 0
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Ist Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Dept Med Oncol, Via P Maroncelli 40, I-47014 Meldola, ItalyIst Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Dept Med Oncol, Via P Maroncelli 40, I-47014 Meldola, Italy
Delmonte, Angelo
Crino, Lucio
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h-index: 0
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Ist Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Dept Med Oncol, Via P Maroncelli 40, I-47014 Meldola, ItalyIst Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Dept Med Oncol, Via P Maroncelli 40, I-47014 Meldola, Italy
机构:
Brown Univ, Warren Alpert Med Sch, Dept Orthopaed, Providence, RI 02903 USA
Brown Univ, Warren Alpert Med Sch, Dept Med, Providence, RI 02903 USA
Rhode Isl Hosp, Ctr Regenerat Med, Providence, RI 02903 USA
Rhode Isl Hosp, Cardiovasc Res Ctr, Providence, RI 02903 USABrown Univ, Warren Alpert Med Sch, Dept Orthopaed, Providence, RI 02903 USA
Gonzalez, David M.
Medici, Damian
论文数: 0引用数: 0
h-index: 0
机构:
Brown Univ, Warren Alpert Med Sch, Dept Orthopaed, Providence, RI 02903 USA
Brown Univ, Warren Alpert Med Sch, Dept Med, Providence, RI 02903 USA
Rhode Isl Hosp, Ctr Regenerat Med, Providence, RI 02903 USA
Rhode Isl Hosp, Cardiovasc Res Ctr, Providence, RI 02903 USABrown Univ, Warren Alpert Med Sch, Dept Orthopaed, Providence, RI 02903 USA
机构:
Univ Turku, Turku Ctr Biotechnol, Turku, Finland
Abo Akad Univ, Turku, FinlandUniv Turku, Turku Ctr Biotechnol, Turku, Finland
Hamidi, Hellyeh
Ivaska, Johanna
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h-index: 0
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Univ Turku, Turku Ctr Biotechnol, Turku, Finland
Abo Akad Univ, Turku, Finland
Univ Turku, Dept Biochem, Turku, FinlandUniv Turku, Turku Ctr Biotechnol, Turku, Finland
机构:
Univ Calif San Francisco, Ctr Regenerat Med & Stem Cell Res, Dept Cell & Tissue Biol & Anat, San Francisco, CA 94143 USA
Univ Calif San Francisco, Ctr Regenerat Med & Stem Cell Res, Dept Eli & Edythe Broad, San Francisco, CA 94143 USAUniv Calif San Francisco, Ctr Regenerat Med & Stem Cell Res, Dept Cell & Tissue Biol & Anat, San Francisco, CA 94143 USA
Lamouille, Samy
Xu, Jian
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h-index: 0
机构:
Univ So Calif, Ctr Craniofacial Mol Biol, Los Angeles, CA 90033 USAUniv Calif San Francisco, Ctr Regenerat Med & Stem Cell Res, Dept Cell & Tissue Biol & Anat, San Francisco, CA 94143 USA
Xu, Jian
Derynck, Rik
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h-index: 0
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Univ Calif San Francisco, Ctr Regenerat Med & Stem Cell Res, Dept Cell & Tissue Biol & Anat, San Francisco, CA 94143 USA
Univ Calif San Francisco, Ctr Regenerat Med & Stem Cell Res, Dept Eli & Edythe Broad, San Francisco, CA 94143 USAUniv Calif San Francisco, Ctr Regenerat Med & Stem Cell Res, Dept Cell & Tissue Biol & Anat, San Francisco, CA 94143 USA
机构:
Ist Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Dept Med Oncol, Via P Maroncelli 40, I-47014 Meldola, ItalyIst Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Dept Med Oncol, Via P Maroncelli 40, I-47014 Meldola, Italy
Bronte, Giuseppe
Bravaccini, Sara
论文数: 0引用数: 0
h-index: 0
机构:
Ist Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Biosci Lab, Meldola, ItalyIst Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Dept Med Oncol, Via P Maroncelli 40, I-47014 Meldola, Italy
Bravaccini, Sara
Bronte, Enrico
论文数: 0引用数: 0
h-index: 0
机构:
Univ Palermo, Dept Surg Oncol & Oral Sci, Palermo, ItalyIst Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Dept Med Oncol, Via P Maroncelli 40, I-47014 Meldola, Italy
Bronte, Enrico
Burgio, Marco Angelo
论文数: 0引用数: 0
h-index: 0
机构:
Ist Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Dept Med Oncol, Via P Maroncelli 40, I-47014 Meldola, ItalyIst Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Dept Med Oncol, Via P Maroncelli 40, I-47014 Meldola, Italy
Burgio, Marco Angelo
Rolfo, Christian
论文数: 0引用数: 0
h-index: 0
机构:
Univ Ziekenhuis Antwerpen, Dept Oncol, Phase Early Clin Trials Unit 1, Edegem, BelgiumIst Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Dept Med Oncol, Via P Maroncelli 40, I-47014 Meldola, Italy
Rolfo, Christian
Delmonte, Angelo
论文数: 0引用数: 0
h-index: 0
机构:
Ist Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Dept Med Oncol, Via P Maroncelli 40, I-47014 Meldola, ItalyIst Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Dept Med Oncol, Via P Maroncelli 40, I-47014 Meldola, Italy
Delmonte, Angelo
Crino, Lucio
论文数: 0引用数: 0
h-index: 0
机构:
Ist Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Dept Med Oncol, Via P Maroncelli 40, I-47014 Meldola, ItalyIst Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Dept Med Oncol, Via P Maroncelli 40, I-47014 Meldola, Italy
机构:
Brown Univ, Warren Alpert Med Sch, Dept Orthopaed, Providence, RI 02903 USA
Brown Univ, Warren Alpert Med Sch, Dept Med, Providence, RI 02903 USA
Rhode Isl Hosp, Ctr Regenerat Med, Providence, RI 02903 USA
Rhode Isl Hosp, Cardiovasc Res Ctr, Providence, RI 02903 USABrown Univ, Warren Alpert Med Sch, Dept Orthopaed, Providence, RI 02903 USA
Gonzalez, David M.
Medici, Damian
论文数: 0引用数: 0
h-index: 0
机构:
Brown Univ, Warren Alpert Med Sch, Dept Orthopaed, Providence, RI 02903 USA
Brown Univ, Warren Alpert Med Sch, Dept Med, Providence, RI 02903 USA
Rhode Isl Hosp, Ctr Regenerat Med, Providence, RI 02903 USA
Rhode Isl Hosp, Cardiovasc Res Ctr, Providence, RI 02903 USABrown Univ, Warren Alpert Med Sch, Dept Orthopaed, Providence, RI 02903 USA
机构:
Univ Turku, Turku Ctr Biotechnol, Turku, Finland
Abo Akad Univ, Turku, FinlandUniv Turku, Turku Ctr Biotechnol, Turku, Finland
Hamidi, Hellyeh
Ivaska, Johanna
论文数: 0引用数: 0
h-index: 0
机构:
Univ Turku, Turku Ctr Biotechnol, Turku, Finland
Abo Akad Univ, Turku, Finland
Univ Turku, Dept Biochem, Turku, FinlandUniv Turku, Turku Ctr Biotechnol, Turku, Finland
机构:
Univ Calif San Francisco, Ctr Regenerat Med & Stem Cell Res, Dept Cell & Tissue Biol & Anat, San Francisco, CA 94143 USA
Univ Calif San Francisco, Ctr Regenerat Med & Stem Cell Res, Dept Eli & Edythe Broad, San Francisco, CA 94143 USAUniv Calif San Francisco, Ctr Regenerat Med & Stem Cell Res, Dept Cell & Tissue Biol & Anat, San Francisco, CA 94143 USA
Lamouille, Samy
Xu, Jian
论文数: 0引用数: 0
h-index: 0
机构:
Univ So Calif, Ctr Craniofacial Mol Biol, Los Angeles, CA 90033 USAUniv Calif San Francisco, Ctr Regenerat Med & Stem Cell Res, Dept Cell & Tissue Biol & Anat, San Francisco, CA 94143 USA
Xu, Jian
Derynck, Rik
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Ctr Regenerat Med & Stem Cell Res, Dept Cell & Tissue Biol & Anat, San Francisco, CA 94143 USA
Univ Calif San Francisco, Ctr Regenerat Med & Stem Cell Res, Dept Eli & Edythe Broad, San Francisco, CA 94143 USAUniv Calif San Francisco, Ctr Regenerat Med & Stem Cell Res, Dept Cell & Tissue Biol & Anat, San Francisco, CA 94143 USA