SPDEF is overexpressed in gastric cancer and triggers cell proliferation by forming a positive regulation loop with FoxM1

Wu, Jing; Qin, Wen; Wang, Ying; Sadik, Arsil; Liu, Jilan; Wang, Yangyang; Song, Ping; Wang, Xiaoyun; Sun, Kaiyue; Zeng, Jiping; Wang, Lixiang

doi:10.1002/jcb.27161

Cited by 19 publications

(14 citation statements)

References 44 publications

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“…SPDEF targets FoxM1 (Forkhead Box M1) promoter activity, which has been proven to be highly expressed in gastric cancer. Wu and colleagues found that SPDEF was overexpressed at the mRNA and protein level in human gastric cancer species [15].…”

Section: Spdef (Sam Pointed Domain Containing Ets Transcription Factomentioning

confidence: 99%

WITHDRAWN: Assessment of DOK7 and SPDEF as Potential Epigenetic Biomarkers in Whole Blood of Patients with Gastric Adenocarcinoma and Intestinal Metaplasia

Moradi

Aleyasin

Rezaii

et al. 2021

Preprint

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BackgroundGastric cancer (GC) is the fifth most prevalent cancer, and intestinal metaplasia (IM) is generally considered a precancerous lesion in the gastric carcinogenesis cascade. DNA methylation is one of the most deeply studied epigenetic modifications. Numerous studies have been shown that aberrant methylation of DOK7, an adaptor protein, and SPDEF, a transcription factor, correlates with carcinogenesis. This study aimed to investigate DNA methylation of DOK7 and SPDEF in the whole blood specimens obtained from patients with IM and GC and normal individual controls to examine the possible implication of epigenetic biomarker for differential diagnosis GC from IM.Material and MethodsBioinformatic analysis, differentially methylated regions (DMR) enrichment analysis, was conducted to detect appropriate epigenetic regions in DOK7 and SPDEF CpGs Island. The methylation of selected CPG regions of DOK7 and SPDEF was assayed on 95 blood samples, including 30 IM patients, 30 GC patients, and 35 normal controls individuals. After DNA extraction, MSRE-PCR was utilized to evaluate the loci methylation level, followed by real-time MSRE-PCR to quantify the region's methylation status.ResultsOur analysis indicated that DOK7 and SPDEF have significant hypermethylation in GC and IM versus the normal specimens. Significant methylation changes were observed for Dok7 between IM (p = 0.03), GC (p < 0.001) cases compared to normal controls. For SPDEF significant hypermethylation results obtained, for GC (p < 0.001) and IM (p = 0.03) cases in comparison to normal controls. Sensitivity and specificity for DOK7 as DNA epigenetic biomarker diagnostic of gastric cancer test were determined by ROC statistical analysis revealed high intermediate sensitivity (73.33 %) and high specificity (97.14 %) methylation changes with p < 0.001. For SPDEF DNA methylation test as GC biomarker by ROC statistical analysis revealed lower sensitivity (36.67 %) but higher specificity (97.14 %) with p < 0.001.ConclusionsThese results suggest that the change in the methylation of DOK7 (AUC = 0.9495) and SPDEF (AUC = 0.8419) is a promising epi-biomarker. For the first time, this study shows blood-based biomarkers DOK7 and SPDEF genes are powerful epi-biomarkers and provide insights into gastric cancer pathogenesis and diagnosis.

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Section: Spdef (Sam Pointed Domain Containing Ets Transcription Factomentioning

confidence: 99%

WITHDRAWN: Assessment of DOK7 and SPDEF as Potential Epigenetic Biomarkers in Whole Blood of Patients with Gastric Adenocarcinoma and Intestinal Metaplasia

Moradi

Aleyasin

Rezaii

et al. 2021

Preprint

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show abstract

“…5 Recent evidence has highlighted the crucial roles of TFs in manipulating GC cells proliferation. 6,7 For example, the TEA domain family member 4 (TEAD4), a component of Hippo signaling pathway, was highly expressed in GC tissues and positively associated with poor outcomes in GC patients. Knockdown of TEAD4 significantly decreased the growth of GC cells both in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

ONECUT2 Accelerates Tumor Proliferation Through Activating ROCK1 Expression in Gastric Cancer

Chen¹,

Chen²,

Sun³

et al. 2020

CMAR

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Background Transcription factors (TFs) are key regulators which control gene expression during cancer initiation and progression. In the current study, we aimed to explore the proliferative function and clinical significance of TFs in gastric cancer (GC). Methods Differential analysis was used to investigate the overall expression difference between normal and tumor tissues of each TF in TCGA-STAD cohort. The quantitative real-time polymerase chain reaction (qRT-PCR) was performed to confirm the mRNA expression of one cut homeobox 2 ( ONECUT2 ) in GC tissues. Western blot analysis was conducted to confirm the protein knockdown efficiency. Cell counting, colony formation, and GC xenograft model assays were performed to confirm the proliferative function of ONECUT2 in GC cells. Gene set enrichment analysis (GESA) and qRT-PCR were conducted to confirm the affected signaling pathways and downstream targets of ONECUT2. Results Our data indicated that a TF named ONECUT2 was highly expressed in GC and correlated with patients’ poor prognosis. Importantly, knockdown of ONECUT2 dramatically decreased GC cells proliferation, whereas overexpression of ONECUT2 promoted carcinogenesis in GC. Kyoto encyclopedia of genes and genomes (KEGG) analysis revealed that the upregulating ONECUT2 induced the activation of Wnt signaling pathway and cell cycle regulation pathway. We further identified that ONECUT2 boosted gastric cancer cell proliferation through enhancing ROCK1 (Rho associated coiled-coil containing protein kinase 1) mRNA expression. High level of ROCK1 expression rescued proliferative behavior of ONECUT2 -deficient GC cells. Conclusion Our findings demonstrated that ONECUT2 promoted GC cells proliferation through activating ROCK1 expression at the DNA level, suggesting that ONECUT2-ROCK1 axis might be a potential therapeutic target in GC.

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“…Besides, ETS1 could regulate cell viability via interfering glycolysis in pancreatic cancer ( 86 ); increased expression of ETS2 promotes drug resistance in colorectal cancer ( 87 ). Interestingly, unlike its tumor-suppressive role in colorectal cancer and HCC, PDEF is overexpressed in gastric cancer and promotes gastric cancer cell proliferation by regulating FoxM1 expression through a positive feedback loop ( 39 , 88 , 89 ). In conclusion, ETS family may offer vast potential for developing novel therapeutic strategies.…”

Section: Discussionmentioning

confidence: 99%

The E-Twenty-Six Family in Hepatocellular Carcinoma: Moving into the Spotlight

et al. 2021

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Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality worldwide. Although therapeutic strategies have recently advanced, tumor metastasis and drug resistance continue to pose challenges in the treatment of HCC. Therefore, new molecular targets are needed to develop novel therapeutic strategies for this cancer. E-twenty-six (ETS) transcription family has been implicated in human malignancies pathogenesis and progression, including leukemia, Ewing sarcoma, gastrointestinal stromal tumors. Recently, increasing studies have expanded its great potential as functional players in other cancers, including HCC. This review focuses primarily on the key functions and molecular mechanisms of ETS factors in HCC. Elucidating these molecular details may provide novel potential therapeutic strategies for cancers.

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SPDEF is overexpressed in gastric cancer and triggers cell proliferation by forming a positive regulation loop with FoxM1

Cited by 19 publications

References 44 publications

WITHDRAWN: Assessment of DOK7 and SPDEF as Potential Epigenetic Biomarkers in Whole Blood of Patients with Gastric Adenocarcinoma and Intestinal Metaplasia

WITHDRAWN: Assessment of DOK7 and SPDEF as Potential Epigenetic Biomarkers in Whole Blood of Patients with Gastric Adenocarcinoma and Intestinal Metaplasia

<p><em>ONECUT2</em> Accelerates Tumor Proliferation Through Activating <em>ROCK1</em> Expression in Gastric Cancer</p>

The E-Twenty-Six Family in Hepatocellular Carcinoma: Moving into the Spotlight

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