Inhibition of CDK9 activity compromises global splicing in prostate cancer cells

Hu, Qiang; Poulose, Ninu; Girmay, Samuel; Helevä, Alma; Doultsinos, Dimitrios; Gondane, Aishwarya; Steele, R.E.; Liu, Xiaozhuo; Loda, Massimo; Liu, Song; Tang, Dean G.; Mills, Ian G.; Itkonen, Harri M.

doi:10.1080/15476286.2021.1983287

Cited by 17 publications

(14 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…STRING analysis of deregulated genes after 24 h NVP2 treatment in TCam2 cells showed a highly compact and significant network comprising proteins such as splicing factor SF3B1, SRSF6, SRSF7, etc., involved in mRNA splicing, mRNA processing and mRNA transport. The importance of CTD phosphorylated RNA Pol II in the splicing process has already been described [ 62 , 63 ]. Further, it has been shown that CDK9 is crucial for full-length transcription, including poly-adenylation and interaction of splicing and export factors with SF3B1, highlighting the role of CDK9 for accurate splicing and mRNA export [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional CDK Inhibitors as Potential Treatment Option for Testicular Germ Cell Tumors

Funke

Düster

Wilson

et al. 2022

Cancers

View full text Add to dashboard Cite

Type II testicular germ cell tumors (TGCT) are the most frequently diagnosed solid malignancy in young men. Up to 15% of patients with metastatic non-seminomas show cisplatin resistance and a very poor survival rate due to lacking treatment options. Transcriptional cyclin-dependent kinases (CDK) have been shown to be effective targets in the treatment of different types of cancer. Here, we investigated the effects of the CDK inhibitors dinaciclib, flavopiridol, YKL-5-124, THZ1, NVP2, SY0351 and THZ531. An XTT viability assay revealed a strong cytotoxic impact of CDK7/12/13 inhibitor SY0351 and CDK9 inhibitor NVP2 on the TGCT wild-type cell lines (2102EP, NCCIT, TCam2) and the cisplatin-resistant cell lines (2102EP-R, NCCIT-R). The CDK7 inhibitor YKL-5-124 showed a strong impact on 2102EP, 2102EP-R, NCCIT and NCCIT-R cell lines, leaving the MPAF control cell line mostly unaffected. FACS-based analysis revealed mild effects on the cell cycle of 2102EP and TCam2 cells after SY0351, YKL-5-124 or NVP2 treatment. Molecular analysis showed a cell-line-specific response for SY0351 and NVP2 inhibition while YKL-5-124 induced similar molecular changes in 2102EP, TCam2 and MPAF cells. Thus, after TGCT subtype determination, CDK inhibitors might be a potential alternative for optimized and individualized therapy independent of chemotherapy sensitivity.

show abstract

Section: Discussionmentioning

confidence: 99%

Transcriptional CDK Inhibitors as Potential Treatment Option for Testicular Germ Cell Tumors

Funke

Düster

Wilson

et al. 2022

Cancers

View full text Add to dashboard Cite

show abstract

“…( A ) All the DEGs from knockdown of O-GlcNAc transferase after 48 h in LNCaP cells were subjected to GSEA to identify the processes affected. The normalized enrichment score assigned by the GSEA algorithm is plotted and the color of the bar depicts the significance (blue: significant; red: non-significant) (data from GSE169090) [ 39 ]. ( B ) The enrichment score of the DEGs belonging to the significant pathway can be plotted using the GSEA enrichment plot.…”

Section: Discussionmentioning

confidence: 99%

Revealing the History and Mystery of RNA-Seq

Gondane

Itkonen

2023

CIMB

Self Cite

View full text Add to dashboard Cite

Advances in RNA-sequencing technologies have led to the development of intriguing experimental setups, a massive accumulation of data, and high demand for tools to analyze it. To answer this demand, computational scientists have developed a myriad of data analysis pipelines, but it is less often considered what the most appropriate one is. The RNA-sequencing data analysis pipeline can be divided into three major parts: data pre-processing, followed by the main and downstream analyses. Here, we present an overview of the tools used in both the bulk RNA-seq and at the single-cell level, with a particular focus on alternative splicing and active RNA synthesis analysis. A crucial part of data pre-processing is quality control, which defines the necessity of the next steps; adapter removal, trimming, and filtering. After pre-processing, the data are finally analyzed using a variety of tools: differential gene expression, alternative splicing, and assessment of active synthesis, the latter requiring dedicated sample preparation. In brief, we describe the commonly used tools in the sample preparation and analysis of RNA-seq data.

show abstract

“…We demonstrated the interaction between ASF1B and CDK9 in hepatocellular carcinoma cells. Recently, some studies have shown that CDK9 plays a key role in prostate cancer (38), breast cancer (39), acute myeloid leukemia (40), hepatocellular carcinoma (41). Shao et al reported that inhibition of CDK9 impaired proliferation and induced apoptosis in HCC cells (41).…”

Section: Discussionmentioning

confidence: 99%

ASF1B Serves as a Potential Therapeutic Target by Influencing Cell Cycle and Proliferation in Hepatocellular Carcinoma

Ouyang

Zhao

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high morbidity and mortality. Therefore, it is very important to find potential biomarkers that can effectively predict the prognosis and progression of HCC. Recent studies have shown that anti-silencing function 1B (ASF1B) may be a new proliferative marker for tumor diagnosis and prognosis. However, the expression and function of ASF1B in hepatocellular carcinoma remain to be determined. In this study, integrated analysis of the Cancer Genome Atlas (TCGA), genotypic tissue expression (GTEx), and Gene Expression Omnibus (GEO) databases revealed that ASF1B was highly expressed in HCC. Kaplan-Meier survival curve showed that elevated ASF1B expression was associated with poor survival in patients with liver cancer. Correlation analysis of immune infiltration suggested that ASF1B expression was significantly correlated with immune cell infiltration in HCC patients. Gene set enrichment analysis (GSEA) indicated that ASF1B regulated the cell cycle, DNA Replication and oocyte meiosis signaling. Our experiments confirmed that ASF1B was highly expressed in HCC tissues and HCC cell lines. Silence of ASF1B inhibited hepatocellular carcinoma cell growth in vitro. Furthermore, ASF1B deficiency induced apoptosis and cell cycle arrest. Mechanistically, ASF1B knockdown reduced the expression of proliferating cell nuclear antigen (PCNA), cyclinB1, cyclinE2 and CDK9.Moreover, ASF1B interacted with CDK9 in HCC cells. Taken together, these results suggest that the oncogenic gene ASF1B could be a target for inhibiting hepatocellular carcinoma cell growth.

show abstract

Inhibition of CDK9 activity compromises global splicing in prostate cancer cells

Cited by 17 publications

References 36 publications

Transcriptional CDK Inhibitors as Potential Treatment Option for Testicular Germ Cell Tumors

Transcriptional CDK Inhibitors as Potential Treatment Option for Testicular Germ Cell Tumors

Revealing the History and Mystery of RNA-Seq

ASF1B Serves as a Potential Therapeutic Target by Influencing Cell Cycle and Proliferation in Hepatocellular Carcinoma

Contact Info

Product

Resources

About