Histone methyltransferase SETD1A interacts with HIF1α to enhance glycolysis and promote cancer progression in gastric cancer

Wu, Jugang; Chai, Hongjuan; Xu, Xin; Yu, Jiwei; Gu, Yu

doi:10.1002/1878-0261.12689

Cited by 36 publications

(34 citation statements)

References 40 publications

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“…In our previous study, we discovered that histone methyltransferase SETD1A interacts with HIF1α to enhance glycolysis and promote GC progression [30]. Therefore, we believe that YTHDF2 has an important role in GC.…”

Section: Discussionmentioning

confidence: 95%

N6-methyladenosine binding protein YTHDF2 predicts better prognosis in patients with gastric cancer

Xu¹,

Zhang²,

Zheng³

et al. 2020

Preprint

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Background: The potential role of N6-methyladenosine (m6A) in cancer progression has received tremendous attention over the past few years. The aim of this study was to evaluate the effect of YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) on the prognosis of patients and its potential role in gastric cancer.Methods: A total of 305 gastric cancer patients with clinical information were identified from the TCGA dataset. Limma package was used to analyze the differential m6A regulators; the Cox regression model was used to determine the risk factor for OS. A 1:1 propensity score matching (PSM) analysis was employed to adjust for the difference in baseline clinicopathological characteristics between the YTHDF2 low and high expression group. The Cox regression analysis was reused to identify the risk factors for overall survival (OS). GO and KEGG analysis were used to explore the potential role and function of YTHDF2 in gastric cancer.Results: Nineteen m6A methylation regulators were expressed in gastric cancer tissues; YTHDF2 was associated with the prognosis of gastric cancer patients. The expression level of YTHDF2, patient age, and tumor stage were independent risk factors for OS. After PSM, YTHDF2 expression led to a relatively better prognosis and stage. Patients in stage IV had a significantly poor prognosis. The expression of YTHDF2 was associated with cancer-related functions and pathways in gastric cancer.Conclusions: The high expression of YTHDF2 can predict a better prognosis of gastric cancer patients. YTHDF2 exerts a critical role in gastric cancer progression.

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Section: Discussionmentioning

confidence: 95%

N6-methyladenosine binding protein YTHDF2 predicts better prognosis in patients with gastric cancer

Xu¹,

Zhang²,

Zheng³

et al. 2020

Preprint

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“…Gastric cancer dataset was obtained from The Cancer Genome Atlas (TCGA). The SCARA5 expression and association were examined by Gene Expression Profiling Interactive Analysis (GEPIA) ( http://gepia.cancer-pku.cn/ ) 12 and UALCAN dataset ( http://ualcan.path.uab.edu/ ). Overall survival of GC patients was detected by Kaplan-Meier Plotter (http://kmplot.…”

Section: Methodsmentioning

confidence: 99%

“…Overall survival of GC patients was detected by Kaplan-Meier Plotter (http://kmplot. com/analysis/) 12 . The GEO dataset included GSE14210, GSE15459, GSE22377, GSE29272, GSE51105.…”

Section: Methodsmentioning

confidence: 99%

SCARA5 inhibits gastric cancer progression via epithelial-mesenchymal transition suppression

Zhang¹,

Liu²,

Wang³

et al. 2021

J. Cancer

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Scavenger receptor class A member 5 (SCARA5) has been reported to be implicated in several types of cancer. However, its biological roles and mechanism of SCARA5 in gastric cancer (GC) have not been elucidated. In the present study, SCARA5 expression was found to be downregulated in GC which was associated with promoter methylation. The protein level of SCARA5 was negatively associated with aggressive clinicopathological characteristics, as well as poor prognosis. Moreover, SCARA5 overexpression markedly suppressed the growth, migration and invasion of GC cell lines in vitro. Furthermore, upregulation of SCARA5 inhibited gastric tumor growth and metastasis in a xenograft model. Mechanistic analysis revealed that SCARA5 suppressed the migration and invasion of GC cells via inhibiting epithelial-mesenchymal transition (EMT) and inactivating MMP-2 and MMP-9. Taken together, these results demonstrated that SCARA5 might play vital roles in the GC genesis and progression and could serve as a potential biomarker for diagnosis and therapeutic target of GC.

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“…The Western blot assay was performed as previously ( Wu et al, 2020a , b ). In brief, cells were lysed by RIPA buffer and centrifuged, the supernatants were collected for Western blot, and 10∼30 μg proteins were separated and transferred onto PVDF membranes.…”

Section: Methodsmentioning

confidence: 99%

“…SETD1A, which methylates H3K4, plays key roles in cancer progression, including in colorectal and breast cancers ( Shilatifard, 2012 ; Salz et al, 2014 , 2015 ; Tajima et al, 2015 ), and sorafenib resistance ( Wu et al, 2020a ). Our previous study reported that SETD1A promotes GC tumorigenesis by enhancing glycolysis ( Wu et al, 2020b ). However, whether SETD1A promotes GC metastasis remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Histone Methyltransferase SETD1A Induces Epithelial-Mesenchymal Transition to Promote Invasion and Metastasis Through Epigenetic Reprogramming of Snail in Gastric Cancer

Chai

Shan

et al. 2021

Front. Cell Dev. Biol.

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Aberrant epigenetic modification induces oncogene expression and promotes cancer development. The histone lysine methyltransferase SETD1A, which specifically methylates histone 3 lysine 4 (H3K4), is involved in tumor growth and metastasis, and its ectopic expression has been detected in aggressive malignancies. Our previous study reported that SETD1A promotes gastric cancer (GC) proliferation and tumorigenesis. However, the function and molecular mechanisms of SETD1A in GC metastasis remain to be elucidated. In this study, we found that overexpression of SETD1A promoted GC migration and invasion, whereas knockdown of SETD1A suppressed GC migration and invasion in vitro. Moreover, knockdown of SETD1A suppressed GC epithelial-mesenchymal transition (EMT) by increasing the expression of epithelial marker E-cadherin and decreasing the expression of mesenchymal markers, including N-cadherin, Fibronectin, Vimentin, and α-smooth muscle actin (α-SMA). Mechanistically, knockdown of SETD1A reduced the EMT key transcriptional factor snail expression. SETD1A was recruited to the promoter of snail, where SETD1A could methylate H3K4. However, knockdown of SETD1A decreased the methylation of H3K4 on the snail promoter. Furthermore, SETD1A could be a coactivator of snail to induce EMT gene expression. Rescue of snail restored SETD1A knockdown-induced GC migration and invasion inhibition. In addition, knockdown of SETD1A suppressed GC metastasis in vivo. In summary, our data revealed that SETD1A mediated the EMT process and induced metastasis through epigenetic reprogramming of snail.

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Histone methyltransferase SETD1A interacts with HIF1α to enhance glycolysis and promote cancer progression in gastric cancer

Cited by 36 publications

References 40 publications

N6-methyladenosine binding protein YTHDF2 predicts better prognosis in patients with gastric cancer

N6-methyladenosine binding protein YTHDF2 predicts better prognosis in patients with gastric cancer

SCARA5 inhibits gastric cancer progression via epithelial-mesenchymal transition suppression

Histone Methyltransferase SETD1A Induces Epithelial-Mesenchymal Transition to Promote Invasion and Metastasis Through Epigenetic Reprogramming of Snail in Gastric Cancer

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