SPRY4 suppresses proliferation and induces apoptosis of colorectal cancer cells by repressing oncogene EZH2

Guo, Jia; Zhu, Huadong; Li, Qiang; Dong, Jianhua; Xiong, Wei; Yu, Kun

doi:10.18632/aging.202859

Cited by 8 publications

(7 citation statements)

References 33 publications

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“…Rather, our COBRA studies indicated that distal promoter regions #1 #2 are hypermethylated in Caco2 and SW480 cells and correlate with decreased SPRY4 protein expression. Convincingly, our findings of SPRY4 distal promoter hypermethylation and decreased protein expression align with Guo et al’s finding of overall decreased SPRY4 expression in SW480 cells [ 41 ]. In fact, in SW480 cells, SPRY4 contains marginally increased 5mC levels in region #1 and is observantly less expressed than in Caco2 cells.…”

Section: Discussionsupporting

confidence: 91%

Sprouty4 is epigenetically upregulated in human colorectal cancer

et al. 2022

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Sprouty4 (SPRY4) has been frequently reported as a tumor suppressor and is therefore downregulated in various cancers. For the first time, we report that SPRY4 is epigenetically upregulated in colorectal cancer (CRC). In this study, we explored DNA methylation and hydroxymethylation levels of SPRY4 in CRC cells and patient samples and correlated these findings with mRNA and protein expression levels. Three loci within the promoter region of SPRY4 were evaluated for 5mC levels in CRC using the combined bisulfite restriction analysis. In addition, hydroxymethylation levels within SPRY4 were measured in CRC patients. Lastly, DNA methylation and mRNA expression data were extracted from CRC patients in multiple high-throughput data repositories like Gene Expression Omnibus and The Cancer Genome Atlas. Combined in vitro and in silico analysis of promoter methylation levels of SPRY4 clearly demonstrates that the distal promoter region undergoes hypomethylation in CRC patients and is associated with increased expression. Moreover, a decrease in gene body hydroxymethylation and an increase in gene body methylation within the coding region of SPRY4 were found in CRC patients and correlated with increased expression. SPRY4 is epigenetically upregulated in CRC by promoter hypomethylation and hypermethylation within the gene body that warrants future investigation of atypical roles of this established tumor suppressor.

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Section: Discussionsupporting

confidence: 91%

Sprouty4 is epigenetically upregulated in human colorectal cancer

et al. 2022

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“…Thus, EZH2 exerts oncogenic functions in solid cancers, such as CRC, and is associated with poor prognosis. 19,31 Since TRIM29 is a ubiquitination-related enzyme that mediates protein stability, we examined its influence on EZH2 stability. We found that overexpression of TRIM29 enhanced EZH2 stability, whereas regular expression of TRIM29 reduced EZH2 stability, consistent with the effect of another E3 ligase TRIM25.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, EZH2 exerts oncogenic functions in solid cancers, such as CRC, and is associated with poor prognosis. 19,31 Since TRIM29 is a ubiquitination-related enzyme…”

Section: Discussionmentioning

confidence: 99%

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TRIM29 promotes the progression of colorectal cancer by suppressing EZH2 degradation

Chen,

Ma,

Zhang

2023

Exp Biol Med (Maywood)

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Colorectal cancer (CRC) is commonly diagnosed at the advanced stage and has a high mortality rate. Tripartite Motif Containing 29 (TRIM29) is an oncogene in numerous malignancies including CRC. However, the molecular mechanism of TRIM29 is largely unknown. In this study, we investigated the biological functions of TRIM29 and the underlying mechanisms. The expression of TRIM29 and Enhancer of Zeste Homolog 2 (EZH2) was predicted using the bioinformatic analysis and measured using a quantitative real-time polymerase chain reaction (PCR) and immunohistochemical assay. The biological functions of TRIM29 were analyzed using a cell counting kit-8, EdU and transwell assays, scratch test, and flow cytometry. The interaction between TRIM29 and EZH2 was assessed using protein immunoprecipitation. The stability of EZH2 was evaluated by treating it with cycloheximide. Our results indicated that TRIM29 levels were upregulated in CRC. Overexpression of TRIM29 promoted CRC cell proliferation and migration and suppressed apoptosis. The opposite result was obtained when TRIM29 was silenced. TRIM29 interacted with EZH2 mechanically and enhanced the protein stability of EZH2. Depletion of EZH2 reversed the effects of TRIM29, regarding its biological behaviors. Moreover, downregulation of TRIM29 inhibited tumor growth and improved the histopathological prognosis. In conclusion, EZH2 interacted with silenced TRIM29 to suppress its stability, thereby inhibiting cell proliferation, migration, and tumor growth, and promoting apoptosis in CRC. Our findings suggested that TRIM29 is a promising target for CRC therapy.

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“…In this study, a clinical prediction model composed of SPRY4, PPP1R14A, MT1A, DES, SEZ6L2, SLC22A3, and CXCL8 genes was constructed. SPRY4 may function as an antitumor gene in CRC, and SPRY4 suppresses CRC progression by inhibiting EZH2 [47]. The pathogenesis of human melanoma involves PPP1R14A, which drives tumorigenesis and Ras activity through the activation of growthpromoting ERM family factor and inhibition of tumor suppressor merlin [48].…”

Section: Discussionmentioning

confidence: 99%

Construction of an Excellent 7 mRNAsi-Related Gene Model Based on Cancer Stem Cells for Predicting Survival Outcome of Cervical Cancer

Liu

Yang

Liang

et al. 2023

Stem Cells International

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Background. Cervical cancer (CC) is one of the most frequent female malignancy. Cancer stem cells (CSCs) positively affect survival outcomes in cancer patients, but in cervical cancer, the mechanism of tumor stem cells is still uncertain. Methods. RNA-seq data and related clinical follow-up of patients suffering from CC were from TCGA. Consensus clustering screened prognostic mRNAsi-related genes and identified molecular subtypes for CC. Based on the overlapping differentially expressed genes (DEGs) in subtypes, we employed LASSO and multivariate Cox regression to screen prognostic-related genes and established the RiskScore system. The patients were grouped by RiskScore, the prognosis was analyzed by the Kaplan-Meier (K-M) curve among the various groups, and the precision of the RiskScore was assessed by the ROC curve. Finally, the potential worth of RiskScore in immunotherapy/chemotherapy response was assessed by evaluating TIDE scores and chemotherapy drug IC 50 values. Results. We noticed that patients with low mRNAsi had a shorter survival and then identified three molecular subtypes (C1-3), with the C1 having the worst prognosis and the lowest mRNAsi. Finally, we identified 7 prognostic-related genes (SPRY4, PPP1R14A, MT1A, DES, SEZ6L2, SLC22A3, and CXCL8) via LASSO and Cox regression analysis. We established a 7-gene model defined RiskScore to predict the prognosis of CC patients. K-M curve indicated that low RiskScore patients had improved prognosis, and ROC curves indicated that RiskScore could precisely direct the prognostic evaluation for those suffering from the cancer. This was also confirmed in the GSE44001 and GSE52903 external cohorts. Patients were more sensitive to immunotherapy if with low RiskScore, and RiskScore exhibited precise assessment ability in predicting response to immunological therapy in CC patients. Conclusion. CC stemness is associated with patient prognosis, and the RiskScore constructed based on stemness characteristics is an independent prognostic index, which is expected to be a guide for immunotherapy, providing a new idea for CC clinical practice.

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SPRY4 suppresses proliferation and induces apoptosis of colorectal cancer cells by repressing oncogene EZH2

Cited by 8 publications

References 33 publications

Sprouty4 is epigenetically upregulated in human colorectal cancer

Sprouty4 is epigenetically upregulated in human colorectal cancer

TRIM29 promotes the progression of colorectal cancer by suppressing EZH2 degradation

Construction of an Excellent 7 mRNAsi-Related Gene Model Based on Cancer Stem Cells for Predicting Survival Outcome of Cervical Cancer

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