CDC7-dependent transcriptional regulation of RAD54L is essential for tumorigenicity and radio-resistance of glioblastoma

Li, Qi; Xie, Wei; Wang, Ning; Li, Chuankun; Wang, Maode

doi:10.1016/j.tranon.2018.01.003

Cited by 17 publications

(15 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5a), we first tested inhibition of the Serine/Threonine Kinase gene (Atm), which had been shown before to prolong survival of mice injected with MLL-ENL cells 49 . Inhibition of the Cell Division Cycle 7 gene (Cdc7) was another promising target due to its involvement in DNA repair 52 and studies suggesting its importance in both solid 53 and liquid cancers 54 . Lactate Dehydrogenase A gene (Ldha) had not been explored in AML but overexpression has been implicated in a range of solid cancers 55,56 .…”

Section: Resultsmentioning

confidence: 99%

Dissecting the early steps of MLL induced leukaemogenic transformation using a mouse model of AML

et al. 2020

View full text Add to dashboard Cite

Leukaemogenic mutations commonly disrupt cellular differentiation and/or enhance proliferation, thus perturbing the regulatory programs that control self-renewal and differentiation of stem and progenitor cells. Translocations involving the Mll1 (Kmt2a) gene generate powerful oncogenic fusion proteins, predominantly affecting infant and paediatric AML and ALL patients. The early stages of leukaemogenic transformation are typically inaccessible from human patients and conventional mouse models. Here, we take advantage of cells conditionally blocked at the multipotent haematopoietic progenitor stage to develop a MLL-r model capturing early cellular and molecular consequences of MLL-ENL expression based on a clear clonal relationship between parental and leukaemic cells. Through a combination of scRNA-seq, ATAC-seq and genome-scale CRISPR-Cas9 screening, we identify pathways and genes likely to drive the early phases of leukaemogenesis. Finally, we demonstrate the broad utility of using matched parental and transformed cells for small molecule inhibitor studies by validating both previously known and other potential therapeutic targets.

show abstract

Section: Resultsmentioning

confidence: 99%

Dissecting the early steps of MLL induced leukaemogenic transformation using a mouse model of AML

et al. 2020

View full text Add to dashboard Cite

show abstract

“…CDC7 is an evolutionarily conserved serine-threonine kinase that regulates G1/S phase transition and DNA replication [ 68 ]. CDC7 expression is high in GBMs, it is required for tumor proliferation, implicated in radio-resistance, invasion and tumor growth [ 69 , 70 ].…”

Section: Discussionmentioning

confidence: 99%

Musashi1 Contribution to Glioblastoma Development via Regulation of a Network of DNA Replication, Cell Cycle and Division Genes

Baroni

Choudhary

et al. 2021

Cancers

View full text Add to dashboard Cite

RNA-binding proteins (RBPs) function as master regulators of gene expression. Alterations in their levels are often observed in tumors with numerous oncogenic RBPs identified in recent years. Musashi1 (Msi1) is an RBP and stem cell gene that controls the balance between self-renewal and differentiation. High Msi1 levels have been observed in multiple tumors including glioblastoma and are often associated with poor patient outcomes and tumor growth. A comprehensive genomic analysis identified a network of cell cycle/division and DNA replication genes and established these processes as Msi1’s core regulatory functions in glioblastoma. Msi1 controls this gene network via two mechanisms: direct interaction and indirect regulation mediated by the transcription factors E2F2 and E2F8. Moreover, glioblastoma lines with Msi1 knockout (KO) displayed increased sensitivity to cell cycle and DNA replication inhibitors. Our results suggest that a drug combination strategy (Msi1 + cell cycle/DNA replication inhibitors) could be a viable route to treat glioblastoma.

show abstract

“… 54 - 58 RAD54 L, plays a key role in DNA repair in some cancers; however, this has not been proven in CC. 59 , 60 TK1 has a key function in DNA synthesis and repair. 61 Increased expression of TK1 is found in solid malignancies, and it has been associated with a poor outcome.…”

Section: Discussionmentioning

confidence: 99%

Screening and Discovery of New Potential Biomarkers and Small Molecule Drugs for Cervical Cancer: A Bioinformatics Analysis

Qiu

Huang

Xiang

et al. 2020

Technol Cancer Res Treat

View full text Add to dashboard Cite

Background: Cervical cancer (CC) is the second most common type of malignant tumor survival rate is low in advanced stage, metastatic, and recurrent CC patients. This study aimed at identifying potential genes and drugs for CC diagnosis and targeting therapies. Methods: Three GEO mRNA microarray datasets of CC tissues and non-cancerous tissues were analyzed for differentially expressed genes (DEGs) by limma package. GO (Gene Ontologies) and KEGG (Kyoto Encyclopedia of Genes and Genomes) were used to explore the relationships between the DEGs. Protein-protein interaction (PPI) of these genes was established by the STRING database. MCODE was used for screening significant modules in the PPI networks to select hub genes. Biochemical mechanisms of the hub genes were investigated with Metascape. GEPIA database was used for validating the core genes. According to these DEGs, molecular candidates for CC were recognized from the CMAP database. Results: We identified 309 overlapping DEGs in the 2 tissue-types. Pathway analysis revealed that the DEGs were involved in cell cycle, DNA replication, and p53 signaling. PPI networks between overlapping DEGs showed 68 high-connectivity DEGs that were chosen as hub genes. The GEPIA database showed that the expression levels of RRM2, CDC45, GINS2, HELLS, KNTC1, MCM2, MYBL2, PCNA, RAD54 L, RFC4, RFC5, TK1, TOP2A, and TYMS in CC tissues were significantly different from those in the healthy tissues and were significantly relevant to the OS of CC. We found 10 small molecules from the CMAP database that could change the trend of gene expression in CC tissues, including piperlongumine and chrysin. Conclusions: The 14 DEGs identified in this study could serve as novel prognosis biomarkers for the detection and forecasting of CC. Small molecule drugs like piperlongumine and chrysin could be potential therapeutic drugs for CC treatment.

show abstract

CDC7-dependent transcriptional regulation of RAD54L is essential for tumorigenicity and radio-resistance of glioblastoma

Cited by 17 publications

References 30 publications

Dissecting the early steps of MLL induced leukaemogenic transformation using a mouse model of AML

Dissecting the early steps of MLL induced leukaemogenic transformation using a mouse model of AML

Musashi1 Contribution to Glioblastoma Development via Regulation of a Network of DNA Replication, Cell Cycle and Division Genes

Screening and Discovery of New Potential Biomarkers and Small Molecule Drugs for Cervical Cancer: A Bioinformatics Analysis

Contact Info

Product

Resources

About