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Property "Has-20abstract" (as page type) with input value "High-2Dgrade-20glioma-20(HGG)-20is-20an-20incurable-20brain-20cancer.-20The-20transcriptomes-20of-20cells-20within-20HGG-20tumors-20are-20highly-20heterogeneous.-20This-20renders-20the-20tumors-20unresponsive-20or-20able-20to-20adapt-20to-20therapeutics-20targeted-20at-20single-20pathways,-20thereby-20causing-20treatment-20failure.-20To-20overcome-20this,-20we-20focused-20on-20cyclin-2Ddependent-20kinase-207-20(CDK7),-20a-20ubiquitously-20expressed-20molecule-20involved-20in-20two-20major-20drivers-20of-20HGG-20pathogenesis:-20cell-20cycle-20progression-20and-20RNA-20polymerase-2DII-2Dbased-20transcription.-20We-20tested-20the-20activity-20of-20THZ1,-20an-20irreversible-20CDK7-20inhibitor,-20on-20patient-2Dderived-20primary-20HGG-20cell-20lines-20and-20-27-27ex-20vivo-27-27-20HGG-20patient-20tissue-20slices,-20using-20proliferation-20assays,-20microarray-20analysis,-20high-2Dresolution-20respirometry,-20cell-20cycle-20analysis-20and-20-27-27in-20vivo-27-27-20tumor-20orthografts.-20The-20cellular-20processes-20affected-20by-20CDK7-20inhibition-20were-20analyzed-20by-20reverse-20transcriptase-2Dquantitative-20PCR,-20western-20blot,-20flow-20cytometry-20and-20immunofluorescence.-20THZ1-20perturbed-20the-20transcriptome-20and-20disabled-20CDK-20activation,-20leading-20to-20cell-20cycle-20arrest-20at-20G2-20and-20DNA-20damage.-20THZ1-20halted-20transcription-20of-20the-20nuclear-2Dencoded-20mitochondrial-20ribosomal-20genes,-20reducing-20mitochondrial-20translation-20and-20oxidative-20respiration.-20It-20also-20inhibited-20the-20expression-20of-20receptor-20tyrosine-20kinases-20such-20as-20epidermal-20growth-20factor-20receptor-20(EGFR)-20and-20platelet-2Dderived-20growth-20factor-20receptor-2Dα-20(PDGFR-2Dα),-20reducing-20signaling-20flux-20through-20the-20AKT,-20extracellular-2Dsignal-2Dregulated-20kinase-201-2F2-20(ERK1-2F2)-20and-20signal-20transducer-20and-20activator-20of-20transcription-203-20(STAT3)-20downstream-20pathways.-20Finally,-20THZ1-20disrupted-20nucleolar,-20Cajal-20body-20and-20nuclear-20speckle-20formation,-20resulting-20in-20reduced-20cytosolic-20translation-20and-20malfunction-20of-20the-20spliceosome-20and-20thus-20leading-20to-20aberrant-20mRNA-20processing.-20These-20findings-20indicate-20that-20CDK7-20is-20crucial-20for-20gliomagenesis,-20validate-20CDK7-20as-20a-20therapeutic-20target-20and-20provide-20new-20insight-20into-20the-20cellular-20processes-20that-20are-20affected-20by-20THZ1-20and-20induce-20antitumor-20activity." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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