The Experts below are selected from a list of 1995 Experts worldwide ranked by ideXlab platform
Max Costa - One of the best experts on this subject based on the ideXlab platform.
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abstract 4403 regulation of SATB2 via mir 31 in ni induced malignant cell transformation
Cancer Research, 2019Co-Authors: Qiao Yi Chen, Ashley Jordan, Jinquan Li, Thomas Kluz, Max CostaAbstract:The special AT-rich DNA binding protein (SATB2) is a nuclear matrix associated protein and an important transcription factor for biological development, gene regulation, and chromatin remodeling. Under normal circumstances, SATB2 is not expressed in most cells, including epithelial cells of the lung. However, aberrant regulation of SATB2 has been found in various types of cancers including lung, colon, prostate, breast, gastric, and liver. Emerging studies have linked the possible role of SATB2 in carcinogenic metal-induced cell transformation. In fact, our previous microarray analysis showed that SATB2 is strongly induced in Ni-transformed cells. As an IARC Class I Human Carcinogen, there is well-established link between chronic nickel exposure and lung cancer; however, despite of considerable research efforts in regards to the epigenetic mechanisms, little is known about the role of microRNAs in Ni-induced carcinogenesis. As post-transcriptional regulators, miRNAs have great importance in maintaining normal cellular development. In particular, miR-31 is one of the most abundant types of miRNAs and commonly studied in disease development, including cancers of the lung, breast, and liver. Previous studies have shown the miR-31 can directly target the homeobox gene SATB, and here we report that miR-31 is capable of regulating SATB2 in Ni-induced tumorigenesis. First, our results confirmed that knocking down SATB2 in Ni-transformed BEAS-2B cells via shRNA significantly reduced the rate of migration, anchorage-independent growth. Notably, compared to scramble control shRNA transfected cells, SATB2 knockdown cells did not generate tumor growth in mice xenograft model. These results highlight the oncogenic role of SATB2 in cell transformation. In addition, our data indicate that both acute Ni-treated and Ni-transformed cells demonstrated significant reduction in miR-31 expression. Furthermore, we show that overexpressing miR-31 in Ni-transformed cells reduced rates of migration, anchorage-independent growth, and cellular invasion, indicating the importance of miR-31 in Ni-induced BEAS-2B cell transformation. Together, our results provide a novel mechanistic pathway for Ni-induced carcinogenesis, and add to the pool of existing research on the implications of SATB2 and miR-31 in tumorigenesis. Citation Format: Qiao Yi Chen, Yusha Zhu, Ashley Jordan, Jinquan Li, Hong Sun, Thomas Kluz, Max Costa. Regulation of SATB2 via miR-31 in Ni-induced malignant cell transformation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4403.
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Deregulation of SATB2 in carcinogenesis with emphasis on miRNA-mediated control.
Carcinogenesis, 2019Co-Authors: Qiao Yi Chen, Thomas L. Des Marais, Max CostaAbstract:The special AT-rich DNA binding protein (SATB2) is a nuclear matrix-associated protein and an important transcription factor for biological development, gene regulation and chromatin remodeling. Aberrant regulation of SATB2 has been found to highly correlate with various types of cancers including lung, colon, prostate, breast, gastric and liver. Recent studies have revealed that a subset of small non-coding RNAs, termed microRNAs (miRNAs), are important regulators of SATB2 function. As post-transcriptional regulators, miRNAs have been found to have fundament importance maintaining normal cellular development. Evidence suggests that multiple miRNAs, including miR-31, miR-34, miR-182, miR-211, miR-599, are capable of regulating SATB2 in cancers of the lung, liver, colon and breast. This review examines the molecular functions of SATB2 and miRNAs in the text of cancer development and potential strategies for cancer therapy with a focus on systemic miRNA delivery.
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role of mir 31 and SATB2 in arsenic induced malignant beas 2b cell transformation
Molecular Carcinogenesis, 2018Co-Authors: Qiao Yi Chen, Ashley Jordan, Jinquan Li, Thomas Kluz, Feng Wu, Thomas L Desmarais, Xiaoru Zhang, Anthony Murphy, Max CostaAbstract:Arsenic is a naturally occurring and highly potent metalloid known to elicit serious public health concerns. Today, approximately 200 million people around the globe are exposed to arsenic-contaminated drinking water at levels greater than the World Health Organization's recommended limit of 10 parts per billion. As a class I human carcinogen, arsenic exposure is known to elicit various cancers, including lung, skin, liver, and kidney. Current evidence suggests that arsenic is capable of inducing both genotoxic and cytotoxic injury, as well as activating epigenetic pathways to induce carcinogenesis. Our study identifies a novel pathway that is implicated in arsenic-induced carcinogenesis. Arsenic down-regulated miRNA-31 and the release of this inhibition caused overexpression of special AT-rich sequence-binding protein 2 (SATB2). Arsenic is known to disrupt miRNA expression, and here we report for the first time that arsenic is capable of inhibiting miR-31 expression. As a direct downstream target of miR-31, SATB2 is a prominent transcription factor, and nuclear matrix binding protein implicated in many types of human diseases including lung cancer. Results from this study show that arsenic induces the overexpressing SATB2 by inhibiting miR-31 expression, which blocks the translation of SATB2 mRNA, since levels of SATB2 mRNA remain the same but protein levels decrease. Overexpression of SATB2 induces malignant transformation of human bronchial epithelial (BEAS-2B) cells indicating the importance of the expression of miR-31 in preventing carcinogenesis by suppressing SATB2 protein levels.
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SATB2 expression increased anchorage independent growth and cell migration in human bronchial epithelial cells
Toxicology and Applied Pharmacology, 2016Co-Authors: Feng Wu, Ashley Jordan, Thomas Kluz, Steven S Shen, Laura Cartularo, Max CostaAbstract:The special AT-rich sequence-binding protein 2 (SATB2) is a protein that binds to the nuclear matrix attachment region of the cell and regulates gene expression by altering chromatin structure. In our previous study, we reported that SATB2 gene expression was induced in human bronchial epithelial BEAS-2B cells transformed by arsenic, chromium, nickel and vanadium. In this study, we show that ectopic expression of SATB2 in the normal human bronchial epithelial cell-line BEAS-2B increased anchorage-independent growth and cell migration, meanwhile, shRNA-mediated knockdown of SATB2 significantly decreased anchorage-independent growth in Ni transformed BEAS-2B cells. RNA sequencing analyses of SATB2 regulated genes revealed the enrichment of those involved in cytoskeleton, cell adhesion and cell-movement pathways. Our evidence supports the hypothesis that SATB2 plays an important role in BEAS-2B cell transformation.
Rudolf Grosschedl - One of the best experts on this subject based on the ideXlab platform.
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SATB2 is required for the development of a spinal exteroceptive microcircuit that modulates limb position
Neuron, 2016Co-Authors: Kathryn L Hilde, Rudolf Grosschedl, Ariel J Levine, Christopher A Hinckley, Marito Hayashi, Jessica M Montgomery, Miriam Gullo, Shawn P Driscoll, Yoshinori Kohwi, Terumi KohwishigematsuAbstract:Motor behaviors such as walking or withdrawing the limb from a painful stimulus rely upon integrative multimodal sensory circuitry to generate appropriate muscle activation patterns. Both the cellular components and the molecular mechanisms that instruct the assembly of the spinal sensorimotor system are poorly understood. Here we characterize the connectivity pattern of a sub-population of lamina V inhibitory sensory relay neurons marked during development by the nuclear matrix and DNA binding factor SATB2 (ISR(SATB2)). ISR(SATB2) neurons receive inputs from multiple streams of sensory information and relay their outputs to motor command layers of the spinal cord. Deletion of the SATB2 transcription factor from ISR(SATB2) neurons perturbs their cellular position, molecular profile, and pre- and post-synaptic connectivity. These alterations are accompanied by abnormal limb hyperflexion responses to mechanical and thermal stimuli and during walking. Thus, SATB2 is a genetic determinant that mediates proper circuit development in a core sensory-to-motor spinal network.
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SATB2 regulates the differentiation of both callosal and subcerebral projection neurons in the developing cerebral cortex
Cerebral Cortex, 2015Co-Authors: Dino P Leone, Gergana Dobreva, Rudolf Grosschedl, Whitney E Heavner, Emily A Ferenczi, John R Huguenard, Susan K McconnellAbstract:The chromatin-remodeling protein SATB2 plays a role in the generation of distinct subtypes of neocortical pyramidal neurons. Previous studies have shown that SATB2 is required for normal development of callosal projection neurons (CPNs), which fail to extend axons callosally in the absence of SATB2 and instead project subcortically. Here we conditionally delete SATB2 from the developing neocortex and find that neurons in the upper layers adopt some electrophysiological properties characteristic of deep layer neurons, but projections from the superficial layers do not contribute to the aberrant subcortical projections seen in SATB2 mutants. Instead, axons from deep layer CPNs descend subcortically in the absence of SATB2. These data demonstrate distinct developmental roles of SATB2 in regulating the fates of upper and deep layer neurons. Unexpectedly, SATB2 mutant brains also display changes in gene expression by subcerebral projection neurons (SCPNs), accompanied by a failure of corticospinal tract (CST) formation. Altering the timing of SATB2 ablation reveals that SCPNs require an early expression of SATB2 for differentiation and extension of the CST, suggesting that early transient expression of SATB2 in these cells plays an essential role in development. Collectively these data show that SATB2 is required by both CPNs and SCPNs for proper differentiation and axon pathfinding.
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a network of genetic repression and derepression specifies projection fates in the developing neocortex
Proceedings of the National Academy of Sciences of the United States of America, 2012Co-Authors: Karpagam Srinivasan, Gergana Dobreva, Rudolf Grosschedl, Terumi Kohwishigematsu, Dino P Leone, Yoshinori Kohwi, Rosalie K Bateson, Susan K McconnellAbstract:Neurons within each layer in the mammalian cortex have stereotypic projections. Four genes—Fezf2, Ctip2, Tbr1, and SATB2—regulate these projection identities. These genes also interact with each other, and it is unclear how these interactions shape the final projection identity. Here we show, by generating double mutants of Fezf2, Ctip2, and SATB2, that cortical neurons deploy a complex genetic switch that uses mutual repression to produce subcortical or callosal projections. We discovered that Tbr1, EphA4, and Unc5H3 are critical downstream targets of SATB2 in callosal fate specification. This represents a unique role for Tbr1, implicated previously in specifying corticothalamic projections. We further show that Tbr1 expression is dually regulated by SATB2 and Ctip2 in layers 2–5. Finally, we show that SATB2 and Fezf2 regulate two disease-related genes, Auts2 (Autistic Susceptibility Gene2) and Bhlhb5 (mutated in Hereditary Spastic Paraplegia), providing a molecular handle to investigate circuit disorders in neurodevelopmental diseases.
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satb1 and SATB2 are dispensable for x chromosome inactivation in mice
Developmental Cell, 2012Co-Authors: Robert Nechanitzky, Amparo Davila, Fabio Savarese, Stefanie Fietze, Rudolf GrosschedlAbstract:Summary Satb1 and SATB2 have been recently described as regulators of embryonic stem (ES) cell pluripotency and as silencing factors in X chromosome inactivation. The influence of the pluripotency machinery on X chromosome inactivation and the lack of an X chromosome inactivation defect in Satb1 −/− and SATB2 −/− mice raise the question of whether or not Satb proteins are directly and/or redundantly involved in this process. Here, we analyzed X chromosome inactivation in fibroblastic cells that were derived from female Satb1 −/− SATB2 −/− embryos. By fluorescence in situ hybridization to visualize Xist RNA and by immunohistochemistry to detect H3K27me3 histone modifications, we found that female Satb1 −/− SATB2 −/− fibroblastic cells contain proper Barr bodies. Moreover, we did not detect an upregulation of X-linked genes, suggesting that Satb proteins are dispensable for X chromosome inactivation in mice.
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roles of SATB2 in osteogenic differentiation and bone regeneration
Tissue Engineering Part A, 2011Co-Authors: Jin Zhang, Rudolf Grosschedl, Qisheng Tu, Terrence Griffin, Hicham Drissi, Pishan Yang, Jake ChenAbstract:Expressed in branchial arches and osteoblast-lineage cells, special AT-rich sequence-binding protein (SATB2) is responsible for preventing craniofacial abnormalities and defects in osteoblast function. In this study, we transduced SATB2 into murine adult stem cells, and found that SATB2 significantly increased expression levels of bone matrix proteins, osteogenic transcription factors, and a potent angiogenic factor, vascular endothelial growth factor. Using an osterix (Osx) promoter-luciferase construct and calvarial cells isolated from runt-related transcription factor 2 (Runx2)-deficient mice, we found that SATB2 upregulates Osx expression independent of Runx2, but synergistically enhances the regulatory effect of Runx2 on Osx promoter. We then transplanted SATB2-overexpressing adult stem cells genetically double-labeled with bone sialoprotein (BSP) promoter-driven luciferase and β-actin promoter-driven enhanced green fluorescent protein into mandibular bone defects. We identified increased luciferase-...
Ashley Jordan - One of the best experts on this subject based on the ideXlab platform.
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abstract 4403 regulation of SATB2 via mir 31 in ni induced malignant cell transformation
Cancer Research, 2019Co-Authors: Qiao Yi Chen, Ashley Jordan, Jinquan Li, Thomas Kluz, Max CostaAbstract:The special AT-rich DNA binding protein (SATB2) is a nuclear matrix associated protein and an important transcription factor for biological development, gene regulation, and chromatin remodeling. Under normal circumstances, SATB2 is not expressed in most cells, including epithelial cells of the lung. However, aberrant regulation of SATB2 has been found in various types of cancers including lung, colon, prostate, breast, gastric, and liver. Emerging studies have linked the possible role of SATB2 in carcinogenic metal-induced cell transformation. In fact, our previous microarray analysis showed that SATB2 is strongly induced in Ni-transformed cells. As an IARC Class I Human Carcinogen, there is well-established link between chronic nickel exposure and lung cancer; however, despite of considerable research efforts in regards to the epigenetic mechanisms, little is known about the role of microRNAs in Ni-induced carcinogenesis. As post-transcriptional regulators, miRNAs have great importance in maintaining normal cellular development. In particular, miR-31 is one of the most abundant types of miRNAs and commonly studied in disease development, including cancers of the lung, breast, and liver. Previous studies have shown the miR-31 can directly target the homeobox gene SATB, and here we report that miR-31 is capable of regulating SATB2 in Ni-induced tumorigenesis. First, our results confirmed that knocking down SATB2 in Ni-transformed BEAS-2B cells via shRNA significantly reduced the rate of migration, anchorage-independent growth. Notably, compared to scramble control shRNA transfected cells, SATB2 knockdown cells did not generate tumor growth in mice xenograft model. These results highlight the oncogenic role of SATB2 in cell transformation. In addition, our data indicate that both acute Ni-treated and Ni-transformed cells demonstrated significant reduction in miR-31 expression. Furthermore, we show that overexpressing miR-31 in Ni-transformed cells reduced rates of migration, anchorage-independent growth, and cellular invasion, indicating the importance of miR-31 in Ni-induced BEAS-2B cell transformation. Together, our results provide a novel mechanistic pathway for Ni-induced carcinogenesis, and add to the pool of existing research on the implications of SATB2 and miR-31 in tumorigenesis. Citation Format: Qiao Yi Chen, Yusha Zhu, Ashley Jordan, Jinquan Li, Hong Sun, Thomas Kluz, Max Costa. Regulation of SATB2 via miR-31 in Ni-induced malignant cell transformation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4403.
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role of mir 31 and SATB2 in arsenic induced malignant beas 2b cell transformation
Molecular Carcinogenesis, 2018Co-Authors: Qiao Yi Chen, Ashley Jordan, Jinquan Li, Thomas Kluz, Feng Wu, Thomas L Desmarais, Xiaoru Zhang, Anthony Murphy, Max CostaAbstract:Arsenic is a naturally occurring and highly potent metalloid known to elicit serious public health concerns. Today, approximately 200 million people around the globe are exposed to arsenic-contaminated drinking water at levels greater than the World Health Organization's recommended limit of 10 parts per billion. As a class I human carcinogen, arsenic exposure is known to elicit various cancers, including lung, skin, liver, and kidney. Current evidence suggests that arsenic is capable of inducing both genotoxic and cytotoxic injury, as well as activating epigenetic pathways to induce carcinogenesis. Our study identifies a novel pathway that is implicated in arsenic-induced carcinogenesis. Arsenic down-regulated miRNA-31 and the release of this inhibition caused overexpression of special AT-rich sequence-binding protein 2 (SATB2). Arsenic is known to disrupt miRNA expression, and here we report for the first time that arsenic is capable of inhibiting miR-31 expression. As a direct downstream target of miR-31, SATB2 is a prominent transcription factor, and nuclear matrix binding protein implicated in many types of human diseases including lung cancer. Results from this study show that arsenic induces the overexpressing SATB2 by inhibiting miR-31 expression, which blocks the translation of SATB2 mRNA, since levels of SATB2 mRNA remain the same but protein levels decrease. Overexpression of SATB2 induces malignant transformation of human bronchial epithelial (BEAS-2B) cells indicating the importance of the expression of miR-31 in preventing carcinogenesis by suppressing SATB2 protein levels.
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Role of miR‐31 and SATB2 in arsenic‐induced malignant BEAS‐2B cell transformation
Molecular Carcinogenesis, 2018Co-Authors: Qiao Yi Chen, Ashley Jordan, Jinquan Li, Thomas Kluz, Feng Wu, Thomas L Desmarais, Xiaoru Zhang, Anthony MurphyAbstract:Arsenic is a naturally occurring and highly potent metalloid known to elicit serious public health concerns. Today, approximately 200 million people around the globe are exposed to arsenic-contaminated drinking water at levels greater than the World Health Organization’s recommended limit of 10 parts per billion. As a class I human carcinogen, arsenic exposure is known to elicit various cancers, including lung, skin, liver, and kidney. Current evidence suggests that arsenic is capable of inducing both genotoxic and cytotoxic injury, as well as activating epigenetic pathways to induce carcinogenesis. Our study identifies a novel pathway that is implicated in arsenic-induced carcinogenesis. Arsenic down-regulated miRNA-31 and the release of this inhibition caused overexpression of special AT-rich sequence-binding protein 2 (SATB2). Arsenic is known to disrupt miRNA expression, and here we report for the first time that arsenic is capable of inhibiting miR-31 expression. As a direct downstream target of miR-31, SATB2 is a prominent transcription factor and nuclear matrix binding protein implicated in many types of human diseases including lung cancer. Results from this study show that arsenic induces the overexpressing SATB2 by inhibiting miR-31 expression, which blocks the translation of SATB2 mRNA, since levels of SATB2 mRNA remain the same but protein levels decrease. Overexpression of SATB2 induces malignant transformation of human bronchial epithelial (BEAS-2B) cells indicating the importance of the expression of miR-31 in preventing carcinogenesis by suppressing SATB2 protein levels.
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SATB2 expression increased anchorage independent growth and cell migration in human bronchial epithelial cells
Toxicology and Applied Pharmacology, 2016Co-Authors: Feng Wu, Ashley Jordan, Thomas Kluz, Steven S Shen, Laura Cartularo, Max CostaAbstract:The special AT-rich sequence-binding protein 2 (SATB2) is a protein that binds to the nuclear matrix attachment region of the cell and regulates gene expression by altering chromatin structure. In our previous study, we reported that SATB2 gene expression was induced in human bronchial epithelial BEAS-2B cells transformed by arsenic, chromium, nickel and vanadium. In this study, we show that ectopic expression of SATB2 in the normal human bronchial epithelial cell-line BEAS-2B increased anchorage-independent growth and cell migration, meanwhile, shRNA-mediated knockdown of SATB2 significantly decreased anchorage-independent growth in Ni transformed BEAS-2B cells. RNA sequencing analyses of SATB2 regulated genes revealed the enrichment of those involved in cytoskeleton, cell adhesion and cell-movement pathways. Our evidence supports the hypothesis that SATB2 plays an important role in BEAS-2B cell transformation.
Thomas Kluz - One of the best experts on this subject based on the ideXlab platform.
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abstract 4403 regulation of SATB2 via mir 31 in ni induced malignant cell transformation
Cancer Research, 2019Co-Authors: Qiao Yi Chen, Ashley Jordan, Jinquan Li, Thomas Kluz, Max CostaAbstract:The special AT-rich DNA binding protein (SATB2) is a nuclear matrix associated protein and an important transcription factor for biological development, gene regulation, and chromatin remodeling. Under normal circumstances, SATB2 is not expressed in most cells, including epithelial cells of the lung. However, aberrant regulation of SATB2 has been found in various types of cancers including lung, colon, prostate, breast, gastric, and liver. Emerging studies have linked the possible role of SATB2 in carcinogenic metal-induced cell transformation. In fact, our previous microarray analysis showed that SATB2 is strongly induced in Ni-transformed cells. As an IARC Class I Human Carcinogen, there is well-established link between chronic nickel exposure and lung cancer; however, despite of considerable research efforts in regards to the epigenetic mechanisms, little is known about the role of microRNAs in Ni-induced carcinogenesis. As post-transcriptional regulators, miRNAs have great importance in maintaining normal cellular development. In particular, miR-31 is one of the most abundant types of miRNAs and commonly studied in disease development, including cancers of the lung, breast, and liver. Previous studies have shown the miR-31 can directly target the homeobox gene SATB, and here we report that miR-31 is capable of regulating SATB2 in Ni-induced tumorigenesis. First, our results confirmed that knocking down SATB2 in Ni-transformed BEAS-2B cells via shRNA significantly reduced the rate of migration, anchorage-independent growth. Notably, compared to scramble control shRNA transfected cells, SATB2 knockdown cells did not generate tumor growth in mice xenograft model. These results highlight the oncogenic role of SATB2 in cell transformation. In addition, our data indicate that both acute Ni-treated and Ni-transformed cells demonstrated significant reduction in miR-31 expression. Furthermore, we show that overexpressing miR-31 in Ni-transformed cells reduced rates of migration, anchorage-independent growth, and cellular invasion, indicating the importance of miR-31 in Ni-induced BEAS-2B cell transformation. Together, our results provide a novel mechanistic pathway for Ni-induced carcinogenesis, and add to the pool of existing research on the implications of SATB2 and miR-31 in tumorigenesis. Citation Format: Qiao Yi Chen, Yusha Zhu, Ashley Jordan, Jinquan Li, Hong Sun, Thomas Kluz, Max Costa. Regulation of SATB2 via miR-31 in Ni-induced malignant cell transformation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4403.
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role of mir 31 and SATB2 in arsenic induced malignant beas 2b cell transformation
Molecular Carcinogenesis, 2018Co-Authors: Qiao Yi Chen, Ashley Jordan, Jinquan Li, Thomas Kluz, Feng Wu, Thomas L Desmarais, Xiaoru Zhang, Anthony Murphy, Max CostaAbstract:Arsenic is a naturally occurring and highly potent metalloid known to elicit serious public health concerns. Today, approximately 200 million people around the globe are exposed to arsenic-contaminated drinking water at levels greater than the World Health Organization's recommended limit of 10 parts per billion. As a class I human carcinogen, arsenic exposure is known to elicit various cancers, including lung, skin, liver, and kidney. Current evidence suggests that arsenic is capable of inducing both genotoxic and cytotoxic injury, as well as activating epigenetic pathways to induce carcinogenesis. Our study identifies a novel pathway that is implicated in arsenic-induced carcinogenesis. Arsenic down-regulated miRNA-31 and the release of this inhibition caused overexpression of special AT-rich sequence-binding protein 2 (SATB2). Arsenic is known to disrupt miRNA expression, and here we report for the first time that arsenic is capable of inhibiting miR-31 expression. As a direct downstream target of miR-31, SATB2 is a prominent transcription factor, and nuclear matrix binding protein implicated in many types of human diseases including lung cancer. Results from this study show that arsenic induces the overexpressing SATB2 by inhibiting miR-31 expression, which blocks the translation of SATB2 mRNA, since levels of SATB2 mRNA remain the same but protein levels decrease. Overexpression of SATB2 induces malignant transformation of human bronchial epithelial (BEAS-2B) cells indicating the importance of the expression of miR-31 in preventing carcinogenesis by suppressing SATB2 protein levels.
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Role of miR‐31 and SATB2 in arsenic‐induced malignant BEAS‐2B cell transformation
Molecular Carcinogenesis, 2018Co-Authors: Qiao Yi Chen, Ashley Jordan, Jinquan Li, Thomas Kluz, Feng Wu, Thomas L Desmarais, Xiaoru Zhang, Anthony MurphyAbstract:Arsenic is a naturally occurring and highly potent metalloid known to elicit serious public health concerns. Today, approximately 200 million people around the globe are exposed to arsenic-contaminated drinking water at levels greater than the World Health Organization’s recommended limit of 10 parts per billion. As a class I human carcinogen, arsenic exposure is known to elicit various cancers, including lung, skin, liver, and kidney. Current evidence suggests that arsenic is capable of inducing both genotoxic and cytotoxic injury, as well as activating epigenetic pathways to induce carcinogenesis. Our study identifies a novel pathway that is implicated in arsenic-induced carcinogenesis. Arsenic down-regulated miRNA-31 and the release of this inhibition caused overexpression of special AT-rich sequence-binding protein 2 (SATB2). Arsenic is known to disrupt miRNA expression, and here we report for the first time that arsenic is capable of inhibiting miR-31 expression. As a direct downstream target of miR-31, SATB2 is a prominent transcription factor and nuclear matrix binding protein implicated in many types of human diseases including lung cancer. Results from this study show that arsenic induces the overexpressing SATB2 by inhibiting miR-31 expression, which blocks the translation of SATB2 mRNA, since levels of SATB2 mRNA remain the same but protein levels decrease. Overexpression of SATB2 induces malignant transformation of human bronchial epithelial (BEAS-2B) cells indicating the importance of the expression of miR-31 in preventing carcinogenesis by suppressing SATB2 protein levels.
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SATB2 expression increased anchorage independent growth and cell migration in human bronchial epithelial cells
Toxicology and Applied Pharmacology, 2016Co-Authors: Feng Wu, Ashley Jordan, Thomas Kluz, Steven S Shen, Laura Cartularo, Max CostaAbstract:The special AT-rich sequence-binding protein 2 (SATB2) is a protein that binds to the nuclear matrix attachment region of the cell and regulates gene expression by altering chromatin structure. In our previous study, we reported that SATB2 gene expression was induced in human bronchial epithelial BEAS-2B cells transformed by arsenic, chromium, nickel and vanadium. In this study, we show that ectopic expression of SATB2 in the normal human bronchial epithelial cell-line BEAS-2B increased anchorage-independent growth and cell migration, meanwhile, shRNA-mediated knockdown of SATB2 significantly decreased anchorage-independent growth in Ni transformed BEAS-2B cells. RNA sequencing analyses of SATB2 regulated genes revealed the enrichment of those involved in cytoskeleton, cell adhesion and cell-movement pathways. Our evidence supports the hypothesis that SATB2 plays an important role in BEAS-2B cell transformation.
Qiao Yi Chen - One of the best experts on this subject based on the ideXlab platform.
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abstract 4403 regulation of SATB2 via mir 31 in ni induced malignant cell transformation
Cancer Research, 2019Co-Authors: Qiao Yi Chen, Ashley Jordan, Jinquan Li, Thomas Kluz, Max CostaAbstract:The special AT-rich DNA binding protein (SATB2) is a nuclear matrix associated protein and an important transcription factor for biological development, gene regulation, and chromatin remodeling. Under normal circumstances, SATB2 is not expressed in most cells, including epithelial cells of the lung. However, aberrant regulation of SATB2 has been found in various types of cancers including lung, colon, prostate, breast, gastric, and liver. Emerging studies have linked the possible role of SATB2 in carcinogenic metal-induced cell transformation. In fact, our previous microarray analysis showed that SATB2 is strongly induced in Ni-transformed cells. As an IARC Class I Human Carcinogen, there is well-established link between chronic nickel exposure and lung cancer; however, despite of considerable research efforts in regards to the epigenetic mechanisms, little is known about the role of microRNAs in Ni-induced carcinogenesis. As post-transcriptional regulators, miRNAs have great importance in maintaining normal cellular development. In particular, miR-31 is one of the most abundant types of miRNAs and commonly studied in disease development, including cancers of the lung, breast, and liver. Previous studies have shown the miR-31 can directly target the homeobox gene SATB, and here we report that miR-31 is capable of regulating SATB2 in Ni-induced tumorigenesis. First, our results confirmed that knocking down SATB2 in Ni-transformed BEAS-2B cells via shRNA significantly reduced the rate of migration, anchorage-independent growth. Notably, compared to scramble control shRNA transfected cells, SATB2 knockdown cells did not generate tumor growth in mice xenograft model. These results highlight the oncogenic role of SATB2 in cell transformation. In addition, our data indicate that both acute Ni-treated and Ni-transformed cells demonstrated significant reduction in miR-31 expression. Furthermore, we show that overexpressing miR-31 in Ni-transformed cells reduced rates of migration, anchorage-independent growth, and cellular invasion, indicating the importance of miR-31 in Ni-induced BEAS-2B cell transformation. Together, our results provide a novel mechanistic pathway for Ni-induced carcinogenesis, and add to the pool of existing research on the implications of SATB2 and miR-31 in tumorigenesis. Citation Format: Qiao Yi Chen, Yusha Zhu, Ashley Jordan, Jinquan Li, Hong Sun, Thomas Kluz, Max Costa. Regulation of SATB2 via miR-31 in Ni-induced malignant cell transformation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4403.
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Deregulation of SATB2 in carcinogenesis with emphasis on miRNA-mediated control.
Carcinogenesis, 2019Co-Authors: Qiao Yi Chen, Thomas L. Des Marais, Max CostaAbstract:The special AT-rich DNA binding protein (SATB2) is a nuclear matrix-associated protein and an important transcription factor for biological development, gene regulation and chromatin remodeling. Aberrant regulation of SATB2 has been found to highly correlate with various types of cancers including lung, colon, prostate, breast, gastric and liver. Recent studies have revealed that a subset of small non-coding RNAs, termed microRNAs (miRNAs), are important regulators of SATB2 function. As post-transcriptional regulators, miRNAs have been found to have fundament importance maintaining normal cellular development. Evidence suggests that multiple miRNAs, including miR-31, miR-34, miR-182, miR-211, miR-599, are capable of regulating SATB2 in cancers of the lung, liver, colon and breast. This review examines the molecular functions of SATB2 and miRNAs in the text of cancer development and potential strategies for cancer therapy with a focus on systemic miRNA delivery.
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role of mir 31 and SATB2 in arsenic induced malignant beas 2b cell transformation
Molecular Carcinogenesis, 2018Co-Authors: Qiao Yi Chen, Ashley Jordan, Jinquan Li, Thomas Kluz, Feng Wu, Thomas L Desmarais, Xiaoru Zhang, Anthony Murphy, Max CostaAbstract:Arsenic is a naturally occurring and highly potent metalloid known to elicit serious public health concerns. Today, approximately 200 million people around the globe are exposed to arsenic-contaminated drinking water at levels greater than the World Health Organization's recommended limit of 10 parts per billion. As a class I human carcinogen, arsenic exposure is known to elicit various cancers, including lung, skin, liver, and kidney. Current evidence suggests that arsenic is capable of inducing both genotoxic and cytotoxic injury, as well as activating epigenetic pathways to induce carcinogenesis. Our study identifies a novel pathway that is implicated in arsenic-induced carcinogenesis. Arsenic down-regulated miRNA-31 and the release of this inhibition caused overexpression of special AT-rich sequence-binding protein 2 (SATB2). Arsenic is known to disrupt miRNA expression, and here we report for the first time that arsenic is capable of inhibiting miR-31 expression. As a direct downstream target of miR-31, SATB2 is a prominent transcription factor, and nuclear matrix binding protein implicated in many types of human diseases including lung cancer. Results from this study show that arsenic induces the overexpressing SATB2 by inhibiting miR-31 expression, which blocks the translation of SATB2 mRNA, since levels of SATB2 mRNA remain the same but protein levels decrease. Overexpression of SATB2 induces malignant transformation of human bronchial epithelial (BEAS-2B) cells indicating the importance of the expression of miR-31 in preventing carcinogenesis by suppressing SATB2 protein levels.
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Role of miR‐31 and SATB2 in arsenic‐induced malignant BEAS‐2B cell transformation
Molecular Carcinogenesis, 2018Co-Authors: Qiao Yi Chen, Ashley Jordan, Jinquan Li, Thomas Kluz, Feng Wu, Thomas L Desmarais, Xiaoru Zhang, Anthony MurphyAbstract:Arsenic is a naturally occurring and highly potent metalloid known to elicit serious public health concerns. Today, approximately 200 million people around the globe are exposed to arsenic-contaminated drinking water at levels greater than the World Health Organization’s recommended limit of 10 parts per billion. As a class I human carcinogen, arsenic exposure is known to elicit various cancers, including lung, skin, liver, and kidney. Current evidence suggests that arsenic is capable of inducing both genotoxic and cytotoxic injury, as well as activating epigenetic pathways to induce carcinogenesis. Our study identifies a novel pathway that is implicated in arsenic-induced carcinogenesis. Arsenic down-regulated miRNA-31 and the release of this inhibition caused overexpression of special AT-rich sequence-binding protein 2 (SATB2). Arsenic is known to disrupt miRNA expression, and here we report for the first time that arsenic is capable of inhibiting miR-31 expression. As a direct downstream target of miR-31, SATB2 is a prominent transcription factor and nuclear matrix binding protein implicated in many types of human diseases including lung cancer. Results from this study show that arsenic induces the overexpressing SATB2 by inhibiting miR-31 expression, which blocks the translation of SATB2 mRNA, since levels of SATB2 mRNA remain the same but protein levels decrease. Overexpression of SATB2 induces malignant transformation of human bronchial epithelial (BEAS-2B) cells indicating the importance of the expression of miR-31 in preventing carcinogenesis by suppressing SATB2 protein levels.