-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
-
Cosmetic Ingredient
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
Editor’s note iNature is China’s largest academic official account.
It is jointly created by the doctoral team of Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
The iNature Talent Official Account is now launched, focusing on talent recruitment, academic progress, scientific research information, interested parties can Long press or scan the QR code below to follow us
.
iNature glioblastoma (GBM) is the deadliest primary brain cancer, characterized by treatment resistance, promoted by GBM stem cells (GSC)
.
On October 6, 2021, Jeremy N.
Rich of the University of Pittsburgh and Charles Spruck of the Sanford Burnham Prebys Institute of Medical Discovery (Qiu Zhixin, Zhao Linju and Shen Jia are the co-first authors) will publish the question online in Cancer Discovery (IF=39.
40).
A research paper on "Transcription Elongation Machinery Is a Druggable Dependency and Potentiates Immunotherapy in Glioblastoma Stem Cells", which explores genes in a large number of patient-derived GSCs, differentiated glioblastoma cells (DGC) and neural stem cells (NSC) Expression and genome-wide CRISPR/Cas9 screening to determine the main regulators of GSC stemness, revealing that the basic transcription status increases with RNA polymerase II-mediated transcription
.
The complex of YY1 and transcribed CDK9 is essential for the survival and maintenance of GSC in vitro and in vivo
.
YY1 interacts with CDK9 to regulate transcription elongation in GSC
.
Genetic or pharmacological targeting of the YY1-CDK9 complex triggers RNA m6A modification-dependent interferon response, reduces regulatory T cell infiltration, and enhances the efficacy of immune checkpoint therapy in glioblastoma
.
Collectively, these results indicate that the YY1-CDK9 transcription extension complex defines a targetable cellular state with active transcription, suppressed interferon response, and immunotherapy resistance in glioblastoma
.
Glioblastoma (GBM, World Health Organization grade IV glioma) is one of the most aggressive and deadly human cancers
.
The treatment options for GBM patients are still ineffective, and only palliative treatment is available
.
GBM shows extensive intratumoral and microenvironment heterogeneity, among which GBM stem cells (GSC) play an important role in the tumor hierarchy
.
GSC, driven by genetic and epigenetic changes, helps tumors continue to grow, invade the normal brain, evade immune surveillance and treatment resistance; therefore, it represents a key target for GBM treatment
.
Recent advances in the analysis of GBM at the bulk cell and single cell level have deciphered the different cell states associated with GSC, which can be regulated by genetic, epigenetic, or microenvironmental factors
.
Although gene-driven changes, such as EGFR amplification, have failed to provide effective treatments in GBM, examination of epigenetic and transcriptional regulation has identified the main regulatory circuits that define the plasticity of the cell state, as well as the immune response in malignant cells
.
The dysregulated transcription program in cancer cells has opened the way for new cancer therapies, such as targeting MYC with BRD4 inhibitors or targeting enhancer-related gene expression with transcriptional cyclin-dependent kinase (CDK) inhibitors
.
Cell cycle-related CDK4/6 has been well studied in cancer
.
However, the transcriptional CDK involved in RNA polymerase (Pol) II-mediated transcriptional regulation, including CDK7, CDK9 and CDK12, has not yet been fully explored as a therapeutic target
.
In the epigenetic rules, the role of chromatin interactions in cancer remains elusive
.
The CCCTC Binding Factor (CTCF) insulator establishes a topological correlation domain (TAD)
.
In gliomas, IDH1 mutations induce hypermethylation to disrupt CTCF binding sites and chromosomal neighborhoods, leading to the interaction between constitutive enhancers and platelet-derived growth factor receptor A (PDGFRA) and subsequent PDGFRA expression Up
.
Yin Yang 1 (YY1) is another structural regulator of the chromatin interaction loop that controls gene expression
.
Disrupted chromosomal neighborhoods and loops in cancer represent potential targets, but how chromatin structural proteins regulate the status of cancer stem cells and therapeutic opportunities are poorly understood
.
Article pattern (picture from Cancer Discovery) Although immune checkpoint inhibitors have changed the treatment of several solid tumors, including brain metastases, their clinical efficacy in GBM has been disappointing
.
Effective strategies for immunomodulation to enhance immunotherapeutic response are not available in GBM
.
Considering the lack of effective treatment in GBM and the inconsistent response to immunotherapy, the study hypothesized that the system-dependent analysis of chromatin regulatory factors in GSC can identify targetable cell states and related subjective appearances related to GBM treatment response Genetic regulator
.
The study explored gene expression and genome-wide CRISPR/Cas9 screening in a large number of patient-derived GSCs, differentiated glioblastoma cells (DGC) and neural stem cells (NSC) to determine the main regulators of GSC stemness and reveal the basics The transcription status of RNA polymerase II-mediated transcription increases
.
The complex of YY1 and transcribed CDK9 is essential for the survival and maintenance of GSC in vitro and in vivo
.
YY1 interacts with CDK9 to regulate transcription elongation in GSC
.
Genetic or pharmacological targeting of the YY1-CDK9 complex triggers RNA m6A modification-dependent interferon response, reduces regulatory T cell infiltration, and enhances the efficacy of immune checkpoint therapy in glioblastoma
.
Collectively, these results indicate that the YY1-CDK9 transcription extension complex defines a targetable cellular state with active transcription, suppressed interferon response, and immunotherapy resistance in glioblastoma
.
Reference message: https://cancerdiscovery.
aacrjournals.
org/content/early/2021/10/05/2159-8290.
CD-20-1848
It is jointly created by the doctoral team of Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
The iNature Talent Official Account is now launched, focusing on talent recruitment, academic progress, scientific research information, interested parties can Long press or scan the QR code below to follow us
.
iNature glioblastoma (GBM) is the deadliest primary brain cancer, characterized by treatment resistance, promoted by GBM stem cells (GSC)
.
On October 6, 2021, Jeremy N.
Rich of the University of Pittsburgh and Charles Spruck of the Sanford Burnham Prebys Institute of Medical Discovery (Qiu Zhixin, Zhao Linju and Shen Jia are the co-first authors) will publish the question online in Cancer Discovery (IF=39.
40).
A research paper on "Transcription Elongation Machinery Is a Druggable Dependency and Potentiates Immunotherapy in Glioblastoma Stem Cells", which explores genes in a large number of patient-derived GSCs, differentiated glioblastoma cells (DGC) and neural stem cells (NSC) Expression and genome-wide CRISPR/Cas9 screening to determine the main regulators of GSC stemness, revealing that the basic transcription status increases with RNA polymerase II-mediated transcription
.
The complex of YY1 and transcribed CDK9 is essential for the survival and maintenance of GSC in vitro and in vivo
.
YY1 interacts with CDK9 to regulate transcription elongation in GSC
.
Genetic or pharmacological targeting of the YY1-CDK9 complex triggers RNA m6A modification-dependent interferon response, reduces regulatory T cell infiltration, and enhances the efficacy of immune checkpoint therapy in glioblastoma
.
Collectively, these results indicate that the YY1-CDK9 transcription extension complex defines a targetable cellular state with active transcription, suppressed interferon response, and immunotherapy resistance in glioblastoma
.
Glioblastoma (GBM, World Health Organization grade IV glioma) is one of the most aggressive and deadly human cancers
.
The treatment options for GBM patients are still ineffective, and only palliative treatment is available
.
GBM shows extensive intratumoral and microenvironment heterogeneity, among which GBM stem cells (GSC) play an important role in the tumor hierarchy
.
GSC, driven by genetic and epigenetic changes, helps tumors continue to grow, invade the normal brain, evade immune surveillance and treatment resistance; therefore, it represents a key target for GBM treatment
.
Recent advances in the analysis of GBM at the bulk cell and single cell level have deciphered the different cell states associated with GSC, which can be regulated by genetic, epigenetic, or microenvironmental factors
.
Although gene-driven changes, such as EGFR amplification, have failed to provide effective treatments in GBM, examination of epigenetic and transcriptional regulation has identified the main regulatory circuits that define the plasticity of the cell state, as well as the immune response in malignant cells
.
The dysregulated transcription program in cancer cells has opened the way for new cancer therapies, such as targeting MYC with BRD4 inhibitors or targeting enhancer-related gene expression with transcriptional cyclin-dependent kinase (CDK) inhibitors
.
Cell cycle-related CDK4/6 has been well studied in cancer
.
However, the transcriptional CDK involved in RNA polymerase (Pol) II-mediated transcriptional regulation, including CDK7, CDK9 and CDK12, has not yet been fully explored as a therapeutic target
.
In the epigenetic rules, the role of chromatin interactions in cancer remains elusive
.
The CCCTC Binding Factor (CTCF) insulator establishes a topological correlation domain (TAD)
.
In gliomas, IDH1 mutations induce hypermethylation to disrupt CTCF binding sites and chromosomal neighborhoods, leading to the interaction between constitutive enhancers and platelet-derived growth factor receptor A (PDGFRA) and subsequent PDGFRA expression Up
.
Yin Yang 1 (YY1) is another structural regulator of the chromatin interaction loop that controls gene expression
.
Disrupted chromosomal neighborhoods and loops in cancer represent potential targets, but how chromatin structural proteins regulate the status of cancer stem cells and therapeutic opportunities are poorly understood
.
Article pattern (picture from Cancer Discovery) Although immune checkpoint inhibitors have changed the treatment of several solid tumors, including brain metastases, their clinical efficacy in GBM has been disappointing
.
Effective strategies for immunomodulation to enhance immunotherapeutic response are not available in GBM
.
Considering the lack of effective treatment in GBM and the inconsistent response to immunotherapy, the study hypothesized that the system-dependent analysis of chromatin regulatory factors in GSC can identify targetable cell states and related subjective appearances related to GBM treatment response Genetic regulator
.
The study explored gene expression and genome-wide CRISPR/Cas9 screening in a large number of patient-derived GSCs, differentiated glioblastoma cells (DGC) and neural stem cells (NSC) to determine the main regulators of GSC stemness and reveal the basics The transcription status of RNA polymerase II-mediated transcription increases
.
The complex of YY1 and transcribed CDK9 is essential for the survival and maintenance of GSC in vitro and in vivo
.
YY1 interacts with CDK9 to regulate transcription elongation in GSC
.
Genetic or pharmacological targeting of the YY1-CDK9 complex triggers RNA m6A modification-dependent interferon response, reduces regulatory T cell infiltration, and enhances the efficacy of immune checkpoint therapy in glioblastoma
.
Collectively, these results indicate that the YY1-CDK9 transcription extension complex defines a targetable cellular state with active transcription, suppressed interferon response, and immunotherapy resistance in glioblastoma
.
Reference message: https://cancerdiscovery.
aacrjournals.
org/content/early/2021/10/05/2159-8290.
CD-20-1848
