Epiplakin1 promotes the progression of esophageal squamous cell carcinoma by activating the <scp>PI3K‐AKT</scp> signaling pathway

Qiao, Zhongshi; Dai, Chengcheng; Wang, Zhiqian; Wang, Zifan; Wang, Zheng; Zhang, Tongsong; Niu, Wen-jing; Ma, Xuexiao

doi:10.1111/1759-7714.14366

Cited by 6 publications

(8 citation statements)

References 32 publications

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“…Regarding EPPK1 , epiplakin1, it is generally known to participate in epidermal growth factor signaling and cell proliferation, as well as cytoskeleton reorganization. Our data showed that EPPK1 expression is associated with short survival, which is partially coherent with previous studies that have shown that EPPK1 expression activates cell proliferation in cervical cancer and esophageal squamous cell carcinoma [ 32 , 33 ]. As for RHOD , ras homolog family member D, our study showed that RHOD expression is associated with short survival, which is partially in accord with a previous study that reported that the RHOD promotor was differentially methylated between pituitary adenoma and normal tissue [ 34 ].…”

Section: Discussionsupporting

confidence: 92%

Tumor Microenvironment and Genes Affecting the Prognosis of Temozolomide-Treated Glioblastoma

Jang

Cheong

Park

et al. 2023

JPM

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Glioblastoma (GBM) is the most frequent primary brain tumor in adults and has a poor prognosis due to its resistance to Temozolomide (TMZ). However, there is limited research regarding the tumor microenvironment and genes related to the prognosis of TMZ-treated GBM patients. This study aimed to identify putative transcriptomic biomarkers with predictive value in patients with GBM who were treated with TMZ. Publicly available datasets from The Cancer Genome Atlas and Gene Expression Omnibus were analyzed using CIBERSORTx and Weighted Gene Co-expression Network Analysis (WGCNA) to obtain types of highly expressed cell types and gene clusters. Differentially Expressed Genes analysis was performed and was intersected with the WGCNA results to obtain a candidate gene list. Cox proportional-hazard survival analysis was performed to acquire genes related to the prognosis of TMZ-treated GBM patients. Inflammatory microglial cells, dendritic cells, myeloid cells, and glioma stem cells were highly expressed in GBM tissue, and ACP7, EPPK1, PCDHA8, RHOD, DRC1, ZIC3, and PRLR were significantly associated with survival. While the listed genes have been previously reported to be related to glioblastoma or other types of cancer, ACP7 was identified as a novel gene related to the prognosis of GBM. These findings may have potential implications for developing a diagnostic tool to predict GBM resistance and optimize treatment decisions.

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Section: Discussionsupporting

confidence: 92%

Tumor Microenvironment and Genes Affecting the Prognosis of Temozolomide-Treated Glioblastoma

Jang

Cheong

Park

et al. 2023

JPM

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“…EPPK1 was reported to be expressed in diverse developmental, progenitor, and regenerative cells, expressly in cervical and bladder cancer cells, 18,20 suggesting that EPPK1 might be a potent regulatory factor in malignancy progression. Furthermore, the abnormally expressed EPPK1 was also verified in esophageal squamous cell carcinoma 22 . In this research, the data demonstrated that EPPK1 was boosted in esophageal cancer tissues and cells.…”

Section: Discussionsupporting

confidence: 56%

“…Furthermore, the abnormally expressed EPPK1 was also verified in esophageal squamous cell carcinoma. 22 In this research, the data demonstrated that EPPK1 was boosted in esophageal cancer tissues and cells. METTL3 could interact with EPPK1 and regulate its expression via m6A modification in esophageal cancer cells.…”

Section: Mettl3 Deficiency Inhibited the Pi3k/akt Pathway By Regulati...mentioning

confidence: 62%

“…More importantly, EPPK1 has the ability to regulate the proliferation of tumor cells 18 . Emerging evidence indicated that EPPK1 was dysregulated in various malignancies, such as bladder urothelial carcinoma, cervical cancer, hepatocellular carcinoma, and esophageal squamous cell carcinoma 19‐22 . However, the functions of EPPK1 on esophageal cancer are still unclear.…”

Section: Introductionmentioning

confidence: 99%

“…18 Emerging evidence indicated that EPPK1 was dysregulated in various malignancies, such as bladder urothelial carcinoma, cervical cancer, hepatocellular carcinoma, and esophageal squamous cell carcinoma. [19][20][21][22] However, the functions of EPPK1 on esophageal cancer are still unclear. This project mainly assessed the expression METTL3 and EPPK1 in esophageal cancer and identified whether EPPK1 acted as a downstream gene of m6A modification mediated by METTL3 in esophageal cancer cells.…”

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confidence: 99%

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METTL3‐mediated m6A modification of EPPK1 to promote the development of esophageal cancer through regulating the PI3K/AKT pathway

Jia,

2024

Environmental Toxicology

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Methyltransferase like 3 (METTL3) has been proved to be involved in the progression of various cancers. In this study, we explored the role of METTL3 and its underlying mechanism in esophageal cancer progression. The mRNA and protein levels of METTL3 and epiplakin1 (EPPK1) were determined using qRT‐PCR and western blot. The proliferative ability was evaluated through 3‐(4,5)‐dimethylthiahiazo (‐z‐y1)‐3,5‐di‐ phenytetrazoliumromide (MTT), colony formation, and EdU assays. Transwell invasion assay and wound‐healing assay were employed for detecting cell invasion and migration, respectively. Cell stemness was evaluated by sphere‐formation assay. Xenograft tumor experiments and immunohistochemistry (IHC) were performed to explore the effects of METTL3 knockdown on tumor growth in vivo. The N6‐methyladenosine (m6A) modification of EPPK1 was analyzed using MeRIP. RNA‐protein immunoprecipitation (RIP) and dual‐luciferase reporter assays were used to verify the relationship between EPPK1 and METTL3. METTL3 was upregulated in esophageal cancer tissues and cells, which was related to the poor prognosis of esophageal cancer patients. Knockdown of METTL3 overtly decreased the proliferative, invasive, migrated abilities, and cell stemness of esophageal cancer cells in vitro. Moreover, depletion of METTL3 also observably suppressed the growth of tumor in vivo. EPPK1 was a direct target of METTL3, and METTL3 could mediate the m6A modification of EPPK1. EPPK1 was downregulated in esophageal cancer tissues and cells, and EPPK1 depletion markedly repressed cell proliferation, invasion, migration, and stemness of esophageal cancer cells. The inhibition effects of METTL3 deficiency on these malignant behaviors were harbored by EPPK1 upregulation in esophageal cancer cells. In addition, METTL3 deficiency reduced EPPK1 expression to inactivate the PI3K/AKT pathway. Our results revealed that METTL3 deficiency regulated the m6A modification of EPPK1 to inhibit the PI3K/AKT pathway, thereby restraining the progression of esophageal cancer.

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Epiplakin1 promotes the progression of esophageal squamous cell carcinoma by activating the PI3K‐AKT signaling pathway

et al. 2022

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Background Epiplakin1 (EPPK1) has been associated with disease progression and unfavorable prognosis of many cancers, but its functional involvement in esophageal squamous cell carcinoma (ESCC) remains to be uncovered. Methods The Quantitative Real‐time PCR (qPCR) assay was employed to determine the expression of EPPK1 in ESCC tissues and cells. CCK‐8 assay, colony forming assay, wound healing assay, and transwell invasion assay were utilized to evaluate the effects of EPPK1 on cell proliferation, migration, and invasion capacity in ESCC cells using small interfering ribonucleic acids. Flow cytometry was performed to estimate the cell apoptotic rate caused by silencing of EPPK1. The proteins related to epithelial‐to‐mesenchymal transition (EMT), apoptosis, and activation of the phosphatidylinositol 3‐kinase/serine threonine protein kinase 1 (PI3K/AKT) signaling pathway were measured by western blot. Results The expression of EPPK1 was dramatically increased in ESCC tissues and cells compared to that in relative controls. Additionally, silencing of EPPK1 suppressed ESCC cell growth, colony formation, migration, invasion, and EMT, while promoting ESCC cell apoptosis. Furthermore, EPPK1 induced ESCC cell progression via mediating the PI3K/AKT signaling pathway. Conclusion EPPK1 promotes ESCC progression by modulating the PI3K/AKT signaling pathway and could serve as a potential target for ESCC treatment.

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Epiplakin1 promotes the progression of esophageal squamous cell carcinoma by activating the PI3K‐AKT signaling pathway

Cited by 6 publications

References 32 publications

Tumor Microenvironment and Genes Affecting the Prognosis of Temozolomide-Treated Glioblastoma

Tumor Microenvironment and Genes Affecting the Prognosis of Temozolomide-Treated Glioblastoma

METTL3‐mediated m6A modification of EPPK1 to promote the development of esophageal cancer through regulating the PI3K/AKT pathway

Epiplakin1 promotes the progression of esophageal squamous cell carcinoma by activating the PI3K‐AKT signaling pathway

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