Dual inhibition of FOXM1 and its compensatory signaling pathway decreased the survival of ovarian cancer cells

Lee, Dae Woo; Lee, WeonSun; Kwon, Miyeon; Lee, Hae Nam

doi:10.3892/or.2020.7845

Cited by 10 publications

(3 citation statements)

References 26 publications

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“…FOXM1 protein levels within the nucleus were decreased by FDI-6 treatment, resulting in the inhibition of cell proliferation, migration, and invasion [ 33 ]. Several studies have examined the anti-cancer effect of FDI-6 on breast and ovarian cancer cells [ 33 , 45 , 46 ]. However, its anti-cancer effect on lung adenocarcinoma cells has not yet been investigated.…”

Section: Discussionmentioning

confidence: 99%

Characterizing and Targeting Genes Regulated by Transcription Factor MYBL2 in Lung Adenocarcinoma Cells

Lee

Yang

et al. 2022

Cancers

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Overexpression of MYBL2 is associated with poor survival of lung adenocarcinoma patients, but the molecular mechanism by which it regulates transcription and carcinogenesis has not yet been elucidated. In this study, we performed ChIP-seq using an MYBL2-targeted antibody and discovered that MYBL2 primarily binds to the promoters of highly expressed genes in lung adenocarcinoma cells. Using a knockdown experiment of MYBL2 and global transcriptome profiling, we identified that over a thousand genes are dysregulated by MYBL2, and MYBL2 acts as a transcriptional activator in lung adenocarcinoma cells. Moreover, we revealed that the binding sites of FOXM1 are largely shared with MYBL2 binding sites, and genes involved in cell cycle phase transitions are regulated by these transcription factors. We furthermore investigated the effect of a previously reported FOXM1 inhibitor, FDI-6, in lung adenocarcinoma cells. We demonstrated that FDI-6 decreases the proliferation of lung adenocarcinoma cells and inhibits the activities of FOXM1 as well as MYBL2. Moreover, we found that genes involved in cell death and cell cycle are inhibited by FDI-6. Overall, our findings suggest that MYBL2 and FOXM1 activate cell cycle genes together, acting as oncogenic transcription factors in lung adenocarcinoma cells, and they are potential treatment targets for the disease.

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Section: Discussionmentioning

confidence: 99%

Characterizing and Targeting Genes Regulated by Transcription Factor MYBL2 in Lung Adenocarcinoma Cells

Lee

Yang

et al. 2022

Cancers

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“…Tipifarnib, a highly selective farnesyltransferase, was reported to induce apoptosis, tumorigenesis cease, and regression of head and neck squamous cell carcinoma in vivo [54]. Also, tipifarnib may reduce the viability of OVCA cells in vitro [55]. Mitomycin C is a well-known antitumor drug that can form deoxyadenosine monoadducts with DNA and block the replication of DNA to impede the proliferation of cancer cell [56].…”

Section: Discussionmentioning

confidence: 99%

Downregulation of the Coiled-Coil Domain Containing 80 and Its Perspective Mechanisms in Ovarian Carcinoma: A Comprehensive Study

Liang

Chen

et al. 2021

International Journal of Genomics

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Introduction. We aimed to explore the downregulation of the coiled-coil domain containing 80 (CCDC80) and its underlying molecular mechanisms in ovarian carcinoma (OVCA). Materials/Methods. Immunohistochemical staining was performed to confirm the expression status of CCDC80 protein. Combining the data from in-house tissue microarrays and high-throughput datasets, we identified the expression level of CCDC80 in OVCA. We utilized cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm and single-sample gene set enrichment analysis (ssGSEA) to explore the relationship between CCDC80 and the tumor microenvironment (TME) landscape in OVCA. Pathway enrichment, function annotation, and transcription factor (TFs) exploration were conducted to study the latent molecular mechanisms. Moreover, the cell line data in the Genomics of Drug Sensitivity in Cancer (GDSC) database was used to discover the relationship between CCDC80 and drug sensitivity. Results. An integrated standard mean difference (SMD) of −0.919 (95% CI: −1.515–0.324, P = 0.002 ) identified the downregulation of CCDC80 in OVCA based on 1048 samples, and the sROC ( AUC = 0.76 ) showed a moderate discriminatory ability of CCDC80 in OVCA. The fraction of infiltrating naive B cells showed significant differences between the high- and low-CCDC80 expression groups. Also, CCDC80-related genes are enriched in the Ras signaling pathway and metabolic of lipid. Nuclear receptor subfamily three group C member 1 (NR3C1) may be an upstream TF of CCDC80, and CCDC80 may be related to the sensitivity of mitocycin C and nilotinib. Conclusion. CCDC80 was downregulated in OVCA and may play a role as a tumor suppressor in OVCA.

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“…FDI-6 inhibition elicited the upregulation of N-Ras, phosphoprotein kinase Cδ (p-PKCδ), and HER3. Combination FDI-6 with tipifarnib (N-Ras inhibitor), rottlerin (p-PKCδ inhibitor), or sapitinib (HER3 inhibitor) decreased the survival of cancer cells ( 128 ). Src and MAPK are activated in HGSOC.…”

Section: Ici-based Combination Immunotherapiesmentioning

confidence: 99%

Efficacy evaluation of multi-immunotherapy in ovarian cancer: From bench to bed

Bian

Zhao

2022

Front. Immunol.

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Ovarian cancer, one of the most common gynecological malignancies, is characterized by high mortality and poor prognosis. Cytoreductive surgery and chemotherapy remain the mainstay of ovarian cancer treatment, and most women experience recurrence after standard care therapies. There is compelling evidence that ovarian cancer is an immunogenic tumor. For example, the accumulation of tumor-infiltrating lymphocytes is associated with increased survival, while increases in immunosuppressive regulatory T cells are correlated with poor clinical outcomes. Therefore, immunotherapies targeting components of the tumor microenvironment have been gradually integrated into the existing treatment options, including immune checkpoint blockade, adoptive cell therapy, and cancer vaccines. Immunotherapies have changed guidelines for maintenance treatment and established a new paradigm in ovarian cancer treatment. Despite single immunotherapies targeting DNA repair mechanisms, immune checkpoints, and angiogenesis bringing inspiring efficacy, only a subset of patients can benefit much from it. Thus, the multi-immunotherapy investigation remains an active area for ovarian cancer treatment. The current review provides an overview of various clinically oriented forms of multi-immunotherapy and explores potentially effective combinational therapies for ovarian cancer.

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Dual inhibition of FOXM1 and its compensatory signaling pathway decreased the survival of ovarian cancer cells

Cited by 10 publications

References 26 publications

Characterizing and Targeting Genes Regulated by Transcription Factor MYBL2 in Lung Adenocarcinoma Cells

Characterizing and Targeting Genes Regulated by Transcription Factor MYBL2 in Lung Adenocarcinoma Cells

Downregulation of the Coiled-Coil Domain Containing 80 and Its Perspective Mechanisms in Ovarian Carcinoma: A Comprehensive Study

Efficacy evaluation of multi-immunotherapy in ovarian cancer: From bench to bed

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