Identification of new octamer transcription factor 1‐target genes upregulated in castration‐resistant prostate cancer

Yamamoto, Shinichiro; Takayama, Ken‐ichi; Obinata, Daisuke; Fujiwara, Kyoko; Ashikari, Daisaku; Takahashi, Satoru; Inoue, Satoshi

doi:10.1111/cas.14183

Cited by 28 publications

(31 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, hypoxia-inducible factor 1-alpha (HIF-1α) binding sites were revealed on the promoter of DLGAP5, indicating that hypoxia plays a modulatory role on DLGAP5 expression (11). These results were further confirmed by Yamamoto et al (48). Eissa et al (11) demonstrated that DLGAP5 was a reliable and promising biomarker for the detection of bladder cancer, and sensitivity of urine cytology was improved when combined with the mRNA expression of DLGAP5.…”

Section: Discussionmentioning

confidence: 84%

Elevated mRNA expression levels of DLGAP5 are associated with poor prognosis in breast cancer

Dong

Zhang

et al. 2020

Oncol Lett

View full text Add to dashboard Cite

Breast cancer is the most commonly diagnosed type of cancer and one of the leading causes of cancer-associated mortality in women. In addition, the underlying molecular mechanisms of the occurrence and development of breast cancer requires further investigation. In the present study, bioinformatics analysis was performed to identify differentially expressed genes (DEGs) between breast cancer and normal breast tissues to investigate the underlying molecular mechanisms. In addition, reverse transcription-quantitative PCR and immunohistochemistry (IHC) were performed to investigate the protein and mRNA expression levels of a specific DEG, discs large-associated protein 5 (DLGAP5). A Cell Counting Kit-8 assay and flow cytometry analysis were used to assess the effects of DLGAP5 on cell proliferation. In total, 85 DEGs were identified in the three Gene Expression Omnibus datasets, including 40 upregulated and 45 downregulated genes. In addition, 30 hub genes were identified following the construction of a protein-protein interaction network, and 28 of the 30 hub genes were established to be indicators of breast cancer prognosis. DLGAP5 was highly expressed in breast cancer specimens, and its expression levels were correlated with clinical stage and lymph node status. In addition, downregulation of DLGAP5 repressed the proliferation of breast cancer MDA-MB-231 cells and induced cell cycle arrest. Additionally, DLGAP5 was identified to be localized in the mitochondria, and the presence of a conserved microtubule-associated proteins 1A/1B light chain 3B-interacting region motif suggested that DLGAP5 may serve a role in mitophagy. The present results demonstrated an association between DLGAP5 expression levels and the clinicopathological characteristics of patients with breast cancer using IHC. In conclusion, DLGAP5 may be a promising target in the diagnosis and treatment of breast cancer.

show abstract

Section: Discussionmentioning

confidence: 84%

Elevated mRNA expression levels of DLGAP5 are associated with poor prognosis in breast cancer

Dong

Zhang

et al. 2020

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…There have been few studies to date investigating the role of OCT1 in ESCC 31 , 32 . OCT1 was shown to act as a positive regulator of ESCC cells in conjunction with signal transducer and activator of transcription 31 .…”

Section: Discussionmentioning

confidence: 99%

“…OCT1 was shown to act as a positive regulator of ESCC cells in conjunction with signal transducer and activator of transcription 31 . It was also suggested that high OCT1 expression enhances drug resistance in prostate cancer cells 32 . Therefore, OCT1 could function as an important regulator for cancer cells and the drug-resistance, however, the detailed of OCT1 function is still not very clearly.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, OCT1 could function as an important regulator for cancer cells and the drug-resistance, however, the detailed of OCT1 function is still not very clearly. In prostate carcinoma cells, OCT1 could function by interacting with GATA binding protein 2 (GATA2), forkhead box A1 (FOXA1), or androgen receptor 32 . Moreover, OCTs transcription factors have been considered to participate in mediating the self-renew or the stemness features of cancerous cells 10 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

DNA methylation integratedly modulates the expression of Pit-Oct-Unt transcription factors in esophageal squamous cell carcinoma

He¹,

Gong²,

Wang³

et al. 2021

J. Cancer

View full text Add to dashboard Cite

Background: Dysregulation of Pit-Oct-Unc family transcription factors has been implicated in esophageal squamous cell carcinoma (ESCC). In this study, we evaluated the expression and promoter methylation status of Octamer (OCT) transcription factor genes in human ESCC clinical specimens to investigate the mechanism underlying this observation along with the clinical significance. Methods: Total DNA or RNA was extracted from ESCC tissue specimens and the mRNA level of genes encoding the transcription factors OCT1, OCT2, OCT3/OCT4, OCT5, OCT7, OCT9, and OCT11 were evaluated by quantitative PCR. The DNA methylation status of gene promoters was assessed by bisulfite pyrosequencing and next-generation sequencing. The relationship between the expression of these transcription factors and ESCC proliferation was investigated in vitro and in vivo with the colony formation assay and a mouse xenograft tumor model, respectively. We also examined the correlation between OCT gene expression and promoter methylation and clinicopathologic characteristics of ESCC. Results: OCT1 was upregulated whereas OCT4 , OCT6 , and OCT11 were downregulated in ESCC compared to non-tumor tissue. OCT2 , OCT7 , and OCT9 were undetected in all samples. OCT1 , OCT6 , and OCT11 levels were negatively correlated with the methylation of their respective promoters, but there was no relationship between OCT4 expression and promoter methylation status. Conclusion: Changes in promoter methylation rate underlie the observed alterations in OCT1 , OCT6 , and OCT11 expression in ESCC, whereas another mechanism is likely responsible for the dysregulation of OCT4.

show abstract

“…ACSL3 in turn increases AKR1C3 (aldo-keto reductase family 1 member C3) expression, enhancing the backdoor pathway of androgen synthesis that confers resistance to abiraterone ( 113 , 114 ). Beyond ACSL3, the genome-wide network of OCT1 target genes in CRPC is enriched in factors such as anillin actin binding protein (ANLN) and DLG associated protein 5 (DLGAP5) that regulate proliferation and migration ( 115 , 116 ).…”

Section: Oct1mentioning

confidence: 99%

Recent Discoveries in the Androgen Receptor Pathway in Castration-Resistant Prostate Cancer

et al. 2020

Self Cite

View full text Add to dashboard Cite

The androgen receptor (AR) is the main therapeutic target in advanced prostate cancer, because it regulates the growth and progression of prostate cancer cells. Patients may undergo multiple lines of AR-directed treatments, including androgen-deprivation therapy, AR signaling inhibitors (abiraterone acetate, enzalutamide, apalutamide, or darolutamide), or combinations of these therapies. Yet, tumors inevitably develop resistance to the successive lines of treatment. The diverse mechanisms of resistance include reactivation of the AR and dysregulation of AR cofactors and collaborative transcription factors (TFs). Further elucidating the nexus between the AR and collaborative TFs may reveal new strategies targeting the AR directly or indirectly, such as targeting BET proteins or OCT1. However, appropriate preclinical models will be required to test the efficacy of these approaches. Fortunately, an increasing variety of patient-derived models, such as xenografts and organoids, are being developed for discovery-based research and preclinical drug screening. Here we review the mechanisms of drug resistance in the AR signaling pathway, the intersection with collaborative TFs, and the use of patient-derived models for novel drug discovery.

show abstract

Identification of new octamer transcription factor 1‐target genes upregulated in castration‐resistant prostate cancer

Cited by 28 publications

References 36 publications

Elevated mRNA expression levels of DLGAP5 are associated with poor prognosis in breast cancer

Elevated mRNA expression levels of DLGAP5 are associated with poor prognosis in breast cancer

DNA methylation integratedly modulates the expression of Pit-Oct-Unt transcription factors in esophageal squamous cell carcinoma

Recent Discoveries in the Androgen Receptor Pathway in Castration-Resistant Prostate Cancer

Contact Info

Product

Resources

About