Similar Datasets
Project description:Effect of CDK12-IN-3 on uterine serous carcinoma cell line
| PRJNA1137326 | ENA
Project description:We describe the epigenetic profiling of the H3K9me2 and HP1a in Drosophila third instar larvae before and after CDK12 depletion by RNA interference (RNAi). Here we show that CDK12 regulates heterochromatin dynamics in Drosophila chromosomes. Depletion of CDK12 induces the increased HP1a and H3K9me2 binding profile on the coding region of euchromatic genes, with the X chromosome being the most affected. These results are consistent with the polytene chromosome immunostaining pattern of HP1a and H3K9me2 after CDK12 knockdown in our initial cytological observations, which show that CDK12 depletion induce heterochromatin spreading on euchromatic arms, especially on the X chromosome. This study describes a novel role of the CDK12 complex in controlling the epigenetic transition between euchromatin and heterochromatin. Examination of the genome-wide H3K9me2 and HP1a binding profile in wildtype larvae (WT) and CDK12-depleted larvae (CDK12-KD). Examination of the genome-wide CDK12 binding profile in wildtype larvae (WT). Twelve independent immunoprecipitations were conducted for each antibody. Two biological replicates were performed.
2015-11-02 | E-GEOD-63011 | biostudies-arrayexpress
Project description:Serous endometrial cancer represents a relative rare entity accounting for about 10% of all diagnosed endometrial cancer, but it is responsible for 40% of endometrial cancer-related deaths. Patients with serous endometrial cancer are often diagnosed at earlier disease stage, but remain at higher risk of recurrence and poorer prognosis when compared stage-for-stage with endometrioid subtype endometrial cancer. Serous endometrial cancers are characterized by marked nuclear atypia and abnormal p53 staining in immunohistochemistry. The mainstay of treatment for newly diagnosed serous endometrial cancer includes a multi-modal therapy with surgery, chemotherapy and/or radiotherapy. Unfortunately, despite these efforts, survival outcomes still remain poor. Recently, The Cancer Genome Atlas (TCGA) Research Network classified all endometrial cancer types into four categories, of which, serous endometrial cancer mostly is found within the "copy number high" group. This group is characterized by the increased cell cycle deregulation (e.g., CCNE1, MYC, PPP2R1A, PIKCA, ERBB2 and CDKN2A) and TP53 mutations (90%). To date, the combination of pembrolizumab and lenvatinib is an effective treatment modality in second-line therapy, with a response rate of 50% in advanced/recurrent serous endometrial cancer. Owing to the unfavorable outcomes of serous endometrial cancer, clinical trials are a priority. At present, ongoing studies are testing novel combinations of various targeted and immunotherapeutic agents in newly diagnosed and advanced/recurrent endometrial cancer - an important strategy for serous endometrial cancer, whereby tumors are usually p53+ and pMMR, making response to PD-1 inhibitor monotherapy unlikely. Here, the rare tumor working group (including members from the European Society of Gynecologic Oncology (ESGO), Gynecologic Cancer Intergroup (GCIG), and Japanese Gynecologic Oncology Group (JGOG)), performed a narrative review reporting on the current landscape of serous endometrial cancer and focusing on standard and emerging therapeutic options for patients affected by this difficult disease.
| S-EPMC9445918 | biostudies-literature
Project description:In a forward genetic screen, we have previously identified a null mutant of Cdk12 that results in alterations in actin dynamics, the axon initial segment and electrophysiology in Drosophila melanogaster. To decipher how Cdk12 may be having these effects, we extracted RNA from pooled Drosophila heads and compared Cdk12-null mutants to controls at the transcriptome level.
2023-01-01 | E-MTAB-12090 | biostudies-arrayexpress
Project description:Anaplastic thyroid carcinoma (ATC) is the most aggressive type of thyroid cancer, with no effective treatment available. Identification of new anti-ATC drugs represents an urgent need. In this study, we find that ATC cells are highly sensitive to THZ531, a potent inhibitor of the transcriptional cyclin-dependent kinase (CDK), CDK12. Cell-based assays demonstrate that CDK12 inhibition significantly impedes cell cycle progression, induces apoptotic cell death, and impairs colony formation in ATC cells. THZ531 causes a loss of elongating RNA polymerase II and suppresses gene expression in ATC cells. An integrative analysis of gene expression profiles and super-enhancer landscape, combining with functional assays, leads to the discovery of two new ATC cancer genes, ZC3H4 and NEMP1. Furthermore, CDK12 inhibition enhances the sensitivity of ATC cells to doxorubicin-mediated chemotherapy. Thus, these findings indicate that CDK12 is a potential therapeutic target for ATC treatment and its inhibition may help to overcome the chemoresistance in patients with ATC
2022-09-19 | GSE137697 | GEO
Project description:Anaplastic thyroid carcinoma (ATC) is the most aggressive type of thyroid cancer, with no effective treatment available. Identification of new anti-ATC drugs represents an urgent need. In this study, we find that ATC cells are highly sensitive to THZ531, a potent inhibitor of the transcriptional cyclin-dependent kinase (CDK), CDK12. Cell-based assays demonstrate that CDK12 inhibition significantly impedes cell cycle progression, induces apoptotic cell death, and impairs colony formation in ATC cells. THZ531 causes a loss of elongating RNA polymerase II and suppresses gene expression in ATC cells. An integrative analysis of gene expression profiles and super-enhancer landscape, combining with functional assays, leads to the discovery of two new ATC cancer genes, ZC3H4 and NEMP1. Furthermore, CDK12 inhibition enhances the sensitivity of ATC cells to doxorubicin-mediated chemotherapy. Thus, these findings indicate that CDK12 is a potential therapeutic target for ATC treatment and its inhibition may help to overcome the chemoresistance in patients with ATC
2022-09-19 | GSE137696 | GEO
Project description:Endometrial cancer is one of the most common gynecologic malignancies, and patients with high grade disease, especially serous papillary subtype (SPEC) are often related to the poor outcomes. Recent genome-wide analyses have revealed that SPEC exhibits gene expression profiles that are distinct from the endometrioid histologic subtype; therefore, it is important to identify the SPEC driver genes or pathways responsible for the inherently aggressive phenotypes and to develop SPEC-specific therapies to target these driver genes or pathways. Through array-based analysis and immunohistochemical staining of human endometrial cancer tissue, STAT1 is identified high expressed, and can distinguish SPEC from other subtypes of endometrial cancer. In vitro and in vivo experiments show STAT1 role as a pro-survival factor in SPEC. STAT1 was identified as a master gene modulating “transcriptional pro-survival pathways” to enhance multiple malignant characteristics These finding may suggest that targeting of STAT1, the SPEC driver gene, may provide the means to improve poor outcomes for patients with SPEC. We used microarrays to clarify the changes of gene expression along with STAT1-siRNA treatment and to confirm whether there are any changes on genes expression related to STAT1 pathway. We also used the microarray data to clarify genes signatures which can distinguish subtype of human endometrial cancers.
2014-03-20 | E-GEOD-56026 | biostudies-arrayexpress
Project description:Determining interaction partners with CDK12 using IP-MS. Capturing global proteome expression changes as a result of CDK12 knockdown.
2017-03-21 | PXD004184 | Pride
Project description:Endometrial cancer is one of the most common gynecologic malignancies, and patients with high grade disease, especially serous papillary subtype (SPEC) are often related to the poor outcomes. Recent genome-wide analyses have revealed that SPEC exhibits gene expression profiles that are distinct from the endometrioid histologic subtype; therefore, it is important to identify the SPEC driver genes or pathways responsible for the inherently aggressive phenotypes and to develop SPEC-specific therapies to target these driver genes or pathways. Through array-based analysis and immunohistochemical staining of human endometrial cancer tissue, STAT1 is identified high expressed, and can distinguish SPEC from other subtypes of endometrial cancer. In vitro and in vivo experiments show STAT1 role as a pro-survival factor in SPEC. STAT1 was identified as a master gene modulating “transcriptional pro-survival pathways” to enhance multiple malignant characteristics These finding may suggest that targeting of STAT1, the SPEC driver gene, may provide the means to improve poor outcomes for patients with SPEC.
2014-03-20 | GSE56026 | GEO
Project description:CDK12 is a transcription-related CDK that is commonly mutated in different types of cancers. In prostate cancer, defective CDK12 has been identified as a new subtype with a worse prognosis and widespread drug resistance. CRPC is a malignant stage of recurrent prostate cancer following treatment, with a higher frequency of CDK12 mutations compared to early-stage prostate cancer. To investigate the impact of CDK12 defects on the overall gene expression in CRPC cells, we used CRISPR-Cas9 technology to generate CDK12 knockout and control C4-2 cell lines, followed by high-throughput transcriptome sequencing (RNA-seq). Our results demonstrate that CDK12 defects affect the expression of numerous genes in CRPC cells, providing insights into the regulatory role of CDK12 in prostate cancer development.
2024-01-17 | GSE246983 | GEO