The Experts below are selected from a list of 1359 Experts worldwide ranked by ideXlab platform

Chunxue Bai - One of the best experts on this subject based on the ideXlab platform.

  • CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A
    BMC cancer, 2020
    Co-Authors: Fanglei Liu, Meiling Zhang, Yuanlin Song, Lin Tong, Jian Zhou, Chunxue Bai
    Abstract:

    Chromodomain helicase DNA-binding protein 4 (CHD4) has been shown to contribute to DNA repair and cell cycle promotion; however, its roles in cancer initiation and progression remain largely unknown. This study aimed to demonstrate the role of CHD4 in the development of non-small cell lung cancer (NSCLC) and determine the potential mechanisms of action. By using immunohistochemistry, the expression levels were evaluated in both cancer and non-cancerous tissues. Subsequently, CHD4 knockdown and overexpression strategies were employed to investigate the effects of CHD4 on cell proliferation, migration, along with the growth and formation of tumors in a xenografts mouse model. The protein expression levels of CHD4, PHF5A and ROCK/RhoA markers were determined by Western blot analysis. Compared with non-cancerous tissues, CHD4 was overexpressed in cancer tissues and CHD4 expression levels were closely related to clinical parameters of NSCLC patients. In H292 and PC-9 cell lines, CHD4 overexpression could promote the proliferative and migratory potential of NSCLC cells. Furthermore, down-regulation of CHD4 could reduce the proliferative and migratory ability in A549 and H1299 cell lines. Meanwhile, knockdown of CHD4 could decrease the tumorigenicity in nude mice. Finally, we demonstrated that one of the mechanisms underlying the promotive effect of CHD4 on NSCLC proliferation and migration may be through its interaction with PHD finger protein 5A (PHF5A) and subsequent activation of the RhoA/ROCK signaling pathway. CHD4, which is highly expressed in cancer tissue, could be an independent prognostic factor for NSCLC patients. CHD4 plays an important role in regulating the proliferative and migratory abilities of NSCLC via likely the RhoA/ROCK pathway by regulating PHF5A.

  • CHD4 mediates proliferation and migration of non small cell lung cancer via the rhoa rock pathway by regulating phf5a
    BMC Cancer, 2020
    Co-Authors: Fanglei Liu, Meiling Zhang, Yuanlin Song, Lin Tong, Jian Zhou, Chunxue Bai
    Abstract:

    Chromodomain helicase DNA-binding protein 4 (CHD4) has been shown to contribute to DNA repair and cell cycle promotion; however, its roles in cancer initiation and progression remain largely unknown. This study aimed to demonstrate the role of CHD4 in the development of non-small cell lung cancer (NSCLC) and determine the potential mechanisms of action. By using immunohistochemistry, the expression levels were evaluated in both cancer and non-cancerous tissues. Subsequently, CHD4 knockdown and overexpression strategies were employed to investigate the effects of CHD4 on cell proliferation, migration, along with the growth and formation of tumors in a xenografts mouse model. The protein expression levels of CHD4, PHF5A and ROCK/RhoA markers were determined by Western blot analysis. Compared with non-cancerous tissues, CHD4 was overexpressed in cancer tissues and CHD4 expression levels were closely related to clinical parameters of NSCLC patients. In H292 and PC-9 cell lines, CHD4 overexpression could promote the proliferative and migratory potential of NSCLC cells. Furthermore, down-regulation of CHD4 could reduce the proliferative and migratory ability in A549 and H1299 cell lines. Meanwhile, knockdown of CHD4 could decrease the tumorigenicity in nude mice. Finally, we demonstrated that one of the mechanisms underlying the promotive effect of CHD4 on NSCLC proliferation and migration may be through its interaction with PHD finger protein 5A (PHF5A) and subsequent activation of the RhoA/ROCK signaling pathway. CHD4, which is highly expressed in cancer tissue, could be an independent prognostic factor for NSCLC patients. CHD4 plays an important role in regulating the proliferative and migratory abilities of NSCLC via likely the RhoA/ROCK pathway by regulating PHF5A.

  • CHD4 is associated with poor prognosis of non-small cell lung cancer patients through promoting tumor cell proliferation
    11.1 Lung Cancer, 2016
    Co-Authors: Fanglei Liu, Jian Zhou, Chunxue Bai
    Abstract:

    Objectives: To investigate the role of CHD4 in the development of non-small-cell lung cancer(NSCLC) and determine the potential mechanisms of action. Methods: Immunohistochemistry was used to detect gene expression in 146 formalin-fixed, paraffin-embedded surgical lung specimens. The correlation of gene expression levels and clinical parameters in NSCLC patients was analyzed. In vitro experiments were performed to confirm the functional roles of the genes. Gene ontology (GO) enrichment analysis, western blot and co-immunoprecipitation assays were used to identify the mechanism by which those genes contribute to NSCLC development. Measurements and Main Results: Compared with non-cancerous tissues, CHD4 was overexpressed in cancer tissues, and its expression level correlated with the malignant progression of NSCLC. CHD4 could be used as an independent factor for NSCLC patient prognosis. Inhibition of CHD4 was observed to reduce the proliferative ability as well as promote the apoptosis rate of the NSCLC cells. Meanwhile, reduced CHD4 expression could induce the cell cycle arrest at G1/S phase transition. We identified that down-regulation of CHD4 could deactivate the RhoA/ROCK signaling pathway, leading to the hypothesis that the CHD4 might promote the development of NSCLC through the regulation of the RhoA/ROCK signaling pathway. Conclusions: These findings highlight an important role of CHD4 in the regulation of proliferative abilities of NSCLC and suggest a potential application of CHD4 in cancer treatment.

Fanglei Liu - One of the best experts on this subject based on the ideXlab platform.

  • CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A
    BMC cancer, 2020
    Co-Authors: Fanglei Liu, Meiling Zhang, Yuanlin Song, Lin Tong, Jian Zhou, Chunxue Bai
    Abstract:

    Chromodomain helicase DNA-binding protein 4 (CHD4) has been shown to contribute to DNA repair and cell cycle promotion; however, its roles in cancer initiation and progression remain largely unknown. This study aimed to demonstrate the role of CHD4 in the development of non-small cell lung cancer (NSCLC) and determine the potential mechanisms of action. By using immunohistochemistry, the expression levels were evaluated in both cancer and non-cancerous tissues. Subsequently, CHD4 knockdown and overexpression strategies were employed to investigate the effects of CHD4 on cell proliferation, migration, along with the growth and formation of tumors in a xenografts mouse model. The protein expression levels of CHD4, PHF5A and ROCK/RhoA markers were determined by Western blot analysis. Compared with non-cancerous tissues, CHD4 was overexpressed in cancer tissues and CHD4 expression levels were closely related to clinical parameters of NSCLC patients. In H292 and PC-9 cell lines, CHD4 overexpression could promote the proliferative and migratory potential of NSCLC cells. Furthermore, down-regulation of CHD4 could reduce the proliferative and migratory ability in A549 and H1299 cell lines. Meanwhile, knockdown of CHD4 could decrease the tumorigenicity in nude mice. Finally, we demonstrated that one of the mechanisms underlying the promotive effect of CHD4 on NSCLC proliferation and migration may be through its interaction with PHD finger protein 5A (PHF5A) and subsequent activation of the RhoA/ROCK signaling pathway. CHD4, which is highly expressed in cancer tissue, could be an independent prognostic factor for NSCLC patients. CHD4 plays an important role in regulating the proliferative and migratory abilities of NSCLC via likely the RhoA/ROCK pathway by regulating PHF5A.

  • CHD4 mediates proliferation and migration of non small cell lung cancer via the rhoa rock pathway by regulating phf5a
    BMC Cancer, 2020
    Co-Authors: Fanglei Liu, Meiling Zhang, Yuanlin Song, Lin Tong, Jian Zhou, Chunxue Bai
    Abstract:

    Chromodomain helicase DNA-binding protein 4 (CHD4) has been shown to contribute to DNA repair and cell cycle promotion; however, its roles in cancer initiation and progression remain largely unknown. This study aimed to demonstrate the role of CHD4 in the development of non-small cell lung cancer (NSCLC) and determine the potential mechanisms of action. By using immunohistochemistry, the expression levels were evaluated in both cancer and non-cancerous tissues. Subsequently, CHD4 knockdown and overexpression strategies were employed to investigate the effects of CHD4 on cell proliferation, migration, along with the growth and formation of tumors in a xenografts mouse model. The protein expression levels of CHD4, PHF5A and ROCK/RhoA markers were determined by Western blot analysis. Compared with non-cancerous tissues, CHD4 was overexpressed in cancer tissues and CHD4 expression levels were closely related to clinical parameters of NSCLC patients. In H292 and PC-9 cell lines, CHD4 overexpression could promote the proliferative and migratory potential of NSCLC cells. Furthermore, down-regulation of CHD4 could reduce the proliferative and migratory ability in A549 and H1299 cell lines. Meanwhile, knockdown of CHD4 could decrease the tumorigenicity in nude mice. Finally, we demonstrated that one of the mechanisms underlying the promotive effect of CHD4 on NSCLC proliferation and migration may be through its interaction with PHD finger protein 5A (PHF5A) and subsequent activation of the RhoA/ROCK signaling pathway. CHD4, which is highly expressed in cancer tissue, could be an independent prognostic factor for NSCLC patients. CHD4 plays an important role in regulating the proliferative and migratory abilities of NSCLC via likely the RhoA/ROCK pathway by regulating PHF5A.

  • CHD4 is associated with poor prognosis of non-small cell lung cancer patients through promoting tumor cell proliferation
    11.1 Lung Cancer, 2016
    Co-Authors: Fanglei Liu, Jian Zhou, Chunxue Bai
    Abstract:

    Objectives: To investigate the role of CHD4 in the development of non-small-cell lung cancer(NSCLC) and determine the potential mechanisms of action. Methods: Immunohistochemistry was used to detect gene expression in 146 formalin-fixed, paraffin-embedded surgical lung specimens. The correlation of gene expression levels and clinical parameters in NSCLC patients was analyzed. In vitro experiments were performed to confirm the functional roles of the genes. Gene ontology (GO) enrichment analysis, western blot and co-immunoprecipitation assays were used to identify the mechanism by which those genes contribute to NSCLC development. Measurements and Main Results: Compared with non-cancerous tissues, CHD4 was overexpressed in cancer tissues, and its expression level correlated with the malignant progression of NSCLC. CHD4 could be used as an independent factor for NSCLC patient prognosis. Inhibition of CHD4 was observed to reduce the proliferative ability as well as promote the apoptosis rate of the NSCLC cells. Meanwhile, reduced CHD4 expression could induce the cell cycle arrest at G1/S phase transition. We identified that down-regulation of CHD4 could deactivate the RhoA/ROCK signaling pathway, leading to the hypothesis that the CHD4 might promote the development of NSCLC through the regulation of the RhoA/ROCK signaling pathway. Conclusions: These findings highlight an important role of CHD4 in the regulation of proliferative abilities of NSCLC and suggest a potential application of CHD4 in cancer treatment.

Jian Zhou - One of the best experts on this subject based on the ideXlab platform.

  • CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A
    BMC cancer, 2020
    Co-Authors: Fanglei Liu, Meiling Zhang, Yuanlin Song, Lin Tong, Jian Zhou, Chunxue Bai
    Abstract:

    Chromodomain helicase DNA-binding protein 4 (CHD4) has been shown to contribute to DNA repair and cell cycle promotion; however, its roles in cancer initiation and progression remain largely unknown. This study aimed to demonstrate the role of CHD4 in the development of non-small cell lung cancer (NSCLC) and determine the potential mechanisms of action. By using immunohistochemistry, the expression levels were evaluated in both cancer and non-cancerous tissues. Subsequently, CHD4 knockdown and overexpression strategies were employed to investigate the effects of CHD4 on cell proliferation, migration, along with the growth and formation of tumors in a xenografts mouse model. The protein expression levels of CHD4, PHF5A and ROCK/RhoA markers were determined by Western blot analysis. Compared with non-cancerous tissues, CHD4 was overexpressed in cancer tissues and CHD4 expression levels were closely related to clinical parameters of NSCLC patients. In H292 and PC-9 cell lines, CHD4 overexpression could promote the proliferative and migratory potential of NSCLC cells. Furthermore, down-regulation of CHD4 could reduce the proliferative and migratory ability in A549 and H1299 cell lines. Meanwhile, knockdown of CHD4 could decrease the tumorigenicity in nude mice. Finally, we demonstrated that one of the mechanisms underlying the promotive effect of CHD4 on NSCLC proliferation and migration may be through its interaction with PHD finger protein 5A (PHF5A) and subsequent activation of the RhoA/ROCK signaling pathway. CHD4, which is highly expressed in cancer tissue, could be an independent prognostic factor for NSCLC patients. CHD4 plays an important role in regulating the proliferative and migratory abilities of NSCLC via likely the RhoA/ROCK pathway by regulating PHF5A.

  • CHD4 mediates proliferation and migration of non small cell lung cancer via the rhoa rock pathway by regulating phf5a
    BMC Cancer, 2020
    Co-Authors: Fanglei Liu, Meiling Zhang, Yuanlin Song, Lin Tong, Jian Zhou, Chunxue Bai
    Abstract:

    Chromodomain helicase DNA-binding protein 4 (CHD4) has been shown to contribute to DNA repair and cell cycle promotion; however, its roles in cancer initiation and progression remain largely unknown. This study aimed to demonstrate the role of CHD4 in the development of non-small cell lung cancer (NSCLC) and determine the potential mechanisms of action. By using immunohistochemistry, the expression levels were evaluated in both cancer and non-cancerous tissues. Subsequently, CHD4 knockdown and overexpression strategies were employed to investigate the effects of CHD4 on cell proliferation, migration, along with the growth and formation of tumors in a xenografts mouse model. The protein expression levels of CHD4, PHF5A and ROCK/RhoA markers were determined by Western blot analysis. Compared with non-cancerous tissues, CHD4 was overexpressed in cancer tissues and CHD4 expression levels were closely related to clinical parameters of NSCLC patients. In H292 and PC-9 cell lines, CHD4 overexpression could promote the proliferative and migratory potential of NSCLC cells. Furthermore, down-regulation of CHD4 could reduce the proliferative and migratory ability in A549 and H1299 cell lines. Meanwhile, knockdown of CHD4 could decrease the tumorigenicity in nude mice. Finally, we demonstrated that one of the mechanisms underlying the promotive effect of CHD4 on NSCLC proliferation and migration may be through its interaction with PHD finger protein 5A (PHF5A) and subsequent activation of the RhoA/ROCK signaling pathway. CHD4, which is highly expressed in cancer tissue, could be an independent prognostic factor for NSCLC patients. CHD4 plays an important role in regulating the proliferative and migratory abilities of NSCLC via likely the RhoA/ROCK pathway by regulating PHF5A.

  • CHD4 is associated with poor prognosis of non-small cell lung cancer patients through promoting tumor cell proliferation
    11.1 Lung Cancer, 2016
    Co-Authors: Fanglei Liu, Jian Zhou, Chunxue Bai
    Abstract:

    Objectives: To investigate the role of CHD4 in the development of non-small-cell lung cancer(NSCLC) and determine the potential mechanisms of action. Methods: Immunohistochemistry was used to detect gene expression in 146 formalin-fixed, paraffin-embedded surgical lung specimens. The correlation of gene expression levels and clinical parameters in NSCLC patients was analyzed. In vitro experiments were performed to confirm the functional roles of the genes. Gene ontology (GO) enrichment analysis, western blot and co-immunoprecipitation assays were used to identify the mechanism by which those genes contribute to NSCLC development. Measurements and Main Results: Compared with non-cancerous tissues, CHD4 was overexpressed in cancer tissues, and its expression level correlated with the malignant progression of NSCLC. CHD4 could be used as an independent factor for NSCLC patient prognosis. Inhibition of CHD4 was observed to reduce the proliferative ability as well as promote the apoptosis rate of the NSCLC cells. Meanwhile, reduced CHD4 expression could induce the cell cycle arrest at G1/S phase transition. We identified that down-regulation of CHD4 could deactivate the RhoA/ROCK signaling pathway, leading to the hypothesis that the CHD4 might promote the development of NSCLC through the regulation of the RhoA/ROCK signaling pathway. Conclusions: These findings highlight an important role of CHD4 in the regulation of proliferative abilities of NSCLC and suggest a potential application of CHD4 in cancer treatment.

Mei-ren Pan - One of the best experts on this subject based on the ideXlab platform.

  • Identification of CHD4-β1 integrin axis as a prognostic marker in triple-negative breast cancer using next-generation sequencing and bioinformatics
    Life sciences, 2019
    Co-Authors: Fu Ou-yang, Mei-ren Pan, Shu-jyuan Chang, Shao-yu Fang, Ming-feng Hou, Chi-wen Luo
    Abstract:

    Abstract Aims Triple-negative breast cancer (TNBC) is a special subtype of breast cancer that lacks receptor expression and is difficult to cure. Epigenetic regulators have been suggested as targets for cancer therapy in recent years. Our previous study indicated that the chromodomain-helicase-DNA-binding protein 4 (CHD4) is a prognostic biomarker of TNBC and therapeutic target in patients with TNBC. However, the exact mechanisms regulated by CHD4 are still unclear. Methods In this study, we compared differences in gene expression in parental and CHD4-deficient cells by next-generation sequencing and Ingenuity Pathway Analysis. Key findings We found that β1 integrin is a downstream target gene of CHD4, which could be transcriptionally regulated by CHD4 in TNBC cells. Consistent with in vitro data, immunohistochemistry revealed that co-expression of β1 integrin and CHD4 was significantly associated with metastatic state, recurrence, and survival status in TNBC patients. It also showed a positive correlation between β1 integrin and CHD4 in vivo. Significance This is the first study to suggest that CHD4 regulates β1 integrin in TNBC. Overall, CHD4-β1 integrin axis could potentially be a predictive marker in patients with TNBC and the use of β1 integrin inhibitors may be a therapeutic option for TNBC patients with high CHD4 expression.

  • The NuRD complex-mediated p21 suppression facilitates chemoresistance in BRCA-proficient breast cancer.
    Experimental cell research, 2017
    Co-Authors: Ming-feng Hou, Chi-wen Luo, Tsung-ming Chang, Wen-chun Hung, Tzu-yi Chen, Ya-li Tsai, Chee-yin Chai, Mei-ren Pan
    Abstract:

    Abstract The Mi-2/nucleosome remodeling and deacetylase (NuRD) complex play a role in silencing gene expression. CHD4, the core component of the NuRD complex, which cooperates with histone deacetylase in reducing tumor suppressor genes (TSGs). To dissect the mechanisms underlying cancer promotion, we clarify the role of CHD4 in cyclin-dependent kinase inhibitor protein p21. Here, our data indicates that CHD4 deficiency impairs the recruitments of HDAC1 to the p21 promoter. ~ 300 bp proximal promoter region is responsible for CHD4-HDAC1 axis-mediated p21 transcriptional activity. For identifying the role of anti-cancer drug response, knockdown of p21 overcomes cisplatin and poly-(ADP-ribose) polymerase (PARP) inhibitor-mediated growth suppression in CHD4-depleted cells. Consistent with in vitro data, tissue of patients and bioinformatics approach also showed positive correlation between CHD4 and p21. Overall, our findings not only identify that CHD4 deficiency preferentially impairs cell survival via increasing the level of p21, but also establishes targeting CHD4 as a potential therapeutic implication in BRCA-proficient breast cancer treatment.

  • chromodomain helicase dna binding protein 4 CHD4 regulates homologous recombination dna repair and its deficiency sensitizes cells to poly adp ribose polymerase parp inhibitor treatment
    Journal of Biological Chemistry, 2012
    Co-Authors: Mei-ren Pan, Hui Dai, Wen-chun Hung, Hui Ju Hsieh, Guang Peng, Shiaw-yih Lin
    Abstract:

    To ensure genome stability, cells have evolved a robust defense mechanism to detect, signal, and repair damaged DNA that is generated by exogenous stressors such as ionizing radiation, endogenous stressors such as free radicals, or normal physiological processes such as DNA replication. Homologous recombination (HR) repair is a critical pathway of repairing DNA double strand breaks, and it plays an essential role in maintaining genomic integrity. Previous studies have shown that BRIT1, also known as MCPH1, is a key regulator of HR repair. Here, we report that chromodomain helicase DNA-binding protein 4 (CHD4) is a novel BRIT1 binding partner that regulates the HR repair process. The BRCA1 C-terminal domains of BRIT1 are required for its interaction with CHD4. Depletion of CHD4 and overexpression of the ATPase-dead form of CHD4 impairs the recruitment of BRIT1 to the DNA damage lesions. As a functional consequence, CHD4 deficiency sensitizes cells to double strand break-inducing agents, reduces the recruitment of HR repair factor BRCA1, and impairs HR repair efficiency. We further demonstrate that CHD4-depleted cells are more sensitive to poly(ADP-ribose) polymerase inhibitor treatment. In response to DNA damage induced by poly(ADP-ribose) polymerase inhibitors, CHD4 deficiency impairs the recruitment of DNA repair proteins BRIT1, BRCA1, and replication protein A at early steps of HR repair. Taken together, our findings identify an important role of CHD4 in controlling HR repair to maintain genome stability and establish the potential therapeutic implications of targeting CHD4 deficiency in tumors.

Chi-wen Luo - One of the best experts on this subject based on the ideXlab platform.

  • Identification of CHD4-β1 integrin axis as a prognostic marker in triple-negative breast cancer using next-generation sequencing and bioinformatics
    Life sciences, 2019
    Co-Authors: Fu Ou-yang, Mei-ren Pan, Shu-jyuan Chang, Shao-yu Fang, Ming-feng Hou, Chi-wen Luo
    Abstract:

    Abstract Aims Triple-negative breast cancer (TNBC) is a special subtype of breast cancer that lacks receptor expression and is difficult to cure. Epigenetic regulators have been suggested as targets for cancer therapy in recent years. Our previous study indicated that the chromodomain-helicase-DNA-binding protein 4 (CHD4) is a prognostic biomarker of TNBC and therapeutic target in patients with TNBC. However, the exact mechanisms regulated by CHD4 are still unclear. Methods In this study, we compared differences in gene expression in parental and CHD4-deficient cells by next-generation sequencing and Ingenuity Pathway Analysis. Key findings We found that β1 integrin is a downstream target gene of CHD4, which could be transcriptionally regulated by CHD4 in TNBC cells. Consistent with in vitro data, immunohistochemistry revealed that co-expression of β1 integrin and CHD4 was significantly associated with metastatic state, recurrence, and survival status in TNBC patients. It also showed a positive correlation between β1 integrin and CHD4 in vivo. Significance This is the first study to suggest that CHD4 regulates β1 integrin in TNBC. Overall, CHD4-β1 integrin axis could potentially be a predictive marker in patients with TNBC and the use of β1 integrin inhibitors may be a therapeutic option for TNBC patients with high CHD4 expression.

  • The NuRD complex-mediated p21 suppression facilitates chemoresistance in BRCA-proficient breast cancer.
    Experimental cell research, 2017
    Co-Authors: Ming-feng Hou, Chi-wen Luo, Tsung-ming Chang, Wen-chun Hung, Tzu-yi Chen, Ya-li Tsai, Chee-yin Chai, Mei-ren Pan
    Abstract:

    Abstract The Mi-2/nucleosome remodeling and deacetylase (NuRD) complex play a role in silencing gene expression. CHD4, the core component of the NuRD complex, which cooperates with histone deacetylase in reducing tumor suppressor genes (TSGs). To dissect the mechanisms underlying cancer promotion, we clarify the role of CHD4 in cyclin-dependent kinase inhibitor protein p21. Here, our data indicates that CHD4 deficiency impairs the recruitments of HDAC1 to the p21 promoter. ~ 300 bp proximal promoter region is responsible for CHD4-HDAC1 axis-mediated p21 transcriptional activity. For identifying the role of anti-cancer drug response, knockdown of p21 overcomes cisplatin and poly-(ADP-ribose) polymerase (PARP) inhibitor-mediated growth suppression in CHD4-depleted cells. Consistent with in vitro data, tissue of patients and bioinformatics approach also showed positive correlation between CHD4 and p21. Overall, our findings not only identify that CHD4 deficiency preferentially impairs cell survival via increasing the level of p21, but also establishes targeting CHD4 as a potential therapeutic implication in BRCA-proficient breast cancer treatment.