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BACKGROUND@#Lung cancer is the malignant tumor with the highest incidence and mortality in China, among which non-small cell lung cancer (NSCLC) accounts for about 80%. Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) targeted therapy has been playing an important role in treatment of NSCLC. However, unavoidable therapeutic resistance significantly limits the clinical efficacy of EGFR-TKI. As a key member of the forkhead box protein family, FOXC1 is aberrantly expressed in NSCLC and involved in NSCLC progression. The aim of this work is to investigate the effect and potential mechanism of FOXC1 on gefitinib resistance in NSCLC.@*METHODS@#Western blot was performed to assess the expression of FOXC1 protein in HCC827/GR cells. Immunohistochemistry (IHC) assays were performed in human NSCLC tissues with gefitinib resistance. HCC827/GR cells were transfected with shRNA specifically targeting FOXC1 mRNA and stable cell lines were established. The effects of FOXC1 on cell viability and apoptosis were analyzed using a new methyl thiazolyl tetrazolium assay (MTS assay) and flow cytometry. Self-renewal ability was determined by mammosphere-formation analysis. Quantitative real-time PCR (qRT-PCR) and Western blot were employed to detect the expression of SOX2, Nanog, OCT4 and CD133. Flow cytometry analysis were further used to detect the level of CD133. IHC assays were used to detect the levels of SOX2 and CD133 in NSCLC tissues with genfitiinb resistance. Correlations of the expressions of FOXC1, CD133 and SOX2 with each other in lung adenocarcinoma samples were analyzed based on The Cancer Genome Atlas (TCGA) database.@*RESULTS@#The expression of FOXC1 is significantly increased in HCC827/GR cells compared with HCC827 cells (P<0.05). IHC results showed FOXC1 was highly expressed in NSCLC tissues with gefitinib resisitance. Knockdown of FOXC1 significantly increased the sensitivity of HCC827/GR cells to gefitinib. The cell viability was decreased and the apoptosis was promoted (P<0.05). Moreover, FOXC1 knockdown apparently inhibited the expression of SOX2 and CD133, and decreased the mammosphere-formation capacity in HCC827/GR cells. In NSCLC tissues with gefitinib resistance, the expressions of SOX2 and CD133 were significantly higher compared with gefitinib-sensitive tissues (P<0.01). Meanwhile, the expressions of FOXC1, CD133 and SOX2 with each other were positively correlated (P<0.05).@*CONCLUSIONS@#FOXC1 could increase gefitinib resitance in NSCLC, by which mechanism is related to the regulation of cancer stem cell properties.
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Ischemic stroke is the second leading cause of death worldwide with limited medications and neuroinflammation was recognized as a critical player in the progression of stroke, but how to control the overactive neuroinflammation is still a long-standing challenge. Here, we designed a novel SIRT6 activator MDL-811 which remarkably inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and primary mouse microglia, which were abolished by silencing SIRT6. RNA-seq screening identified the forkhead box C1 (
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Objective To investigate the Influence of FOXC1 downregulating on biological behavior of nasopharyngeal carcinoma (NPC) 5-8F cell lines. Methods Western blotting was used to detect the protein levels of FOXC1 in human immortalized nasopharyngeal cell lines NP69, nasopharyngeal carcinoma cell lines 6-10B with lower metastasis potential and nasopharyngeal carcinoma cell lines 5-8F with higher metastasis potential. siRNA was used to downregulate the expression of FOXC1 in 5-8F cell lines, and then ability of migration and invasion were observed. Results FOXC1 protein expression level in NP69 cell lines, 6-10B cell lines and 5-8F cell lines were (0.27 ± 0.04), (0.7 ± 20.06), (1.08 ± 0.05) respectively, and the difference was statistically significant (P < 0.05). Also ability of cell migration and invasion significantly weakened after FOXC1 depletion in 5-8F cell lines (P < 0.05). Conclusion FOXC1 might regulate invasion and metastasis of nasopharyngeal carcinoma through changing expression of Fibronectin and Vimentin, and FOXC1 may be an available target for molecular target therapy of nasopharyngeal carcinoma.
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Objective To investigate the relationship of clinical pathological features and FOXC1 expression in NPC tissues.Methods 101 cases of nasopharyngeal tissues and 64 cases of chronic inflammatory nasopharyngeal mucosa tissue were selected and detected by immunohistochemistry SP method,and the relationship between the ex-pression of FOXC1 and the clinical pathological features were analyzed.Results The expression of Foxc1 in nasopha-ryngeal carcinoma and nasopharyngeal mucosa inflammatory tissue mainly located in the nucleus,the positive expres-sion rate (84.16%)in nasopharyngeal carcinoma (NPC)was significantly higher than that in chronic nasopharynge-al mucosa (44.44%),(χ2 =65.213,P<0.05).There was no significant relationship among FOXC1 positive expres-sion and sex,age,and clinical stage.FOXC1 positive expression with lymph node metastasis was higher than that with-out lymph node metastasis.Conclusion The expression of FOXC1 in nasopharyngeal carcinoma tissues is significant-ly up-regulated,which may play an important role in the development of nasopharyngeal carcinoma,and has a guid-ing significance for clinical diagnosis of nasopharyngeal carcinoma.
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Axenfeld-Rieger syndrome (ARS) is characterized by anomalies of the anterior segment of the eye and systemic abnormalities. Mutations in the FOXC1 and PITX2 genes are underlying causes of ARS, but there has been few reports on genetically confirmed ARS in Korea. We identified a novel PITX2 mutation (c.300_301delinsT) in 2 Korean patients from a family with ARS. We expand the spectrum of PITX2 mutations and, to the best of our knowledge, this is the first confirmed family of PITX2-related ARS in Korea.
Subject(s)
Adult , Child, Preschool , Female , Humans , Anterior Eye Segment/abnormalities , Base Sequence , Eye Abnormalities/genetics , Heterozygote , Homeodomain Proteins/chemistry , Mutation , Pedigree , Republic of Korea , Transcription Factors/chemistryABSTRACT
Objective:To investingate potential correlations between FOXC1 expression and clinicopathologic features of endometrial cancer and cervical cancer.Methods:FOXC1 protein expression in 54 cases of cervical cancer and 23 of endometrial cancer were investigated with immunohistochemistry.Results:FOXC1 protein expression was observed in cancer tissues,including both endometrial and cervical cancer.Positive FOXC1 expression was revealed in 20(87.0%)of endometrial cancer and 29(53.7%)of cervical cancer.Significant correlation in retrospective study was observed between FOXC1 protein expression and histological grades(P0.05).Conclusion:FOXC1 may play a role in tumorigenesis of cervical cancer.FOXC1 may have no correlation with tumorigenesis of endometrial cancer.