SEC61G overexpression and DNA amplification correlates with prognosis and immune cell infiltration in head and neck squamous cell carcinoma

Lu, Tianzhu; Gong, Xiaomeng; Guo, Qiaojuan; Lin, Canyang; Li, Qingfeng; Tu, Ziwei; Pan, Jianji; Li, Jingao

doi:10.1002/cam4.4301

Cited by 13 publications

(13 citation statements)

References 35 publications

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“…Sec61 translocon gamma subunit (SEC61G) protein is over-expressed in different kinds of cancer and enhances tumor cell growth [ 31 ]. Silencing of this protein blocks AKT survival signaling, thus, playing an anticancer role.…”

Section: Resultsmentioning

confidence: 99%

“…Cancer cells show a high rate of proliferation, and SEC61G is one of the main genes involved, acting as proto-oncogene and enhancing cancer cell survival [ 44 , 47 ]. It is observed that by knocking it out, EGFR/AKT survival signaling, and tumor growth are inhibited [ 31 ]. To the best of our knowledge, no authors describe the interaction between SEC61G and the EC system, but in this study, we observe a reduction in the transcription of SEC61G after the selective stimulation of CB2, thus, suggesting a correlation between them.…”

Section: Discussionmentioning

confidence: 99%

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Effect of CB2 Stimulation on Gene Expression in Pediatric B-Acute Lymphoblastic Leukemia: New Possible Targets

Punzo¹,

Argenziano²,

Tortora³

et al. 2022

IJMS

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Acute lymphoblastic leukemia type B (B-ALL) is the most common kind of pediatric leukemia, characterized by the clonal proliferation of type B lymphoid stem cells. Important progress in ALL treatments led to improvements in long-term survival; nevertheless, many adverse long-term consequences still concern the medical community. Molecular and cellular target therapies, together with immunotherapy, are promising strategies to overcome these concerns. Cannabinoids, enzymes involved in their metabolism, and cannabinoid receptors type 1 (CB1) and type 2 (CB2) constitute the endocannabinoid system, involved in inflammation, immune response, and cancer. CB2 receptor stimulation exerts anti-proliferative and anti-invasive effects in many tumors. In this study, we evaluated the effects of CB2 stimulation on B-ALL cell lines, SUP-B15, by RNA sequencing, Western blotting, and ELISA. We observe a lower expression of CB2 in SUP-B15 cells compared to lymphocytes from healthy subjects, hypothesizing its involvement in B-ALL pathogenesis. CB2 stimulation reduces the expression of CD9, SEC61G, TBX21, and TMSB4X genes involved in tumor growth and progression, and also negatively affects downstream intracellular pathways. Our findings suggest an antitumor role of CB2 stimulation in B-ALL, and highlight a functional correlation between CB2 receptors and specific anti-tumoral pathways, even though further investigations are needed.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of CB2 Stimulation on Gene Expression in Pediatric B-Acute Lymphoblastic Leukemia: New Possible Targets

Punzo¹,

Argenziano²,

Tortora³

et al. 2022

IJMS

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“…Alterations in SEC61 alpha (SEC61A1) and gamma (SEC61G) subunits have been associated with disease. 47–50 Altered SEC61A1 expression or function of SEC61A1 expression has been linked to diabetes mellitus, polycystic kidney disease, and immunodeficiency, whereas reduced SEC61A1 expression is associated with a decrease in ER calcium leak. 49,51,52 Increased SEC61G has been reported in multiple solid organ malignancies, and is thought to promote cancer development, progression, and metastasis.…”

Section: Discussionmentioning

confidence: 99%

Identification of SEC61B as a novel regulator of calcium flux and platelet hyperreactivity in diabetes mellitus

Kong,

Rehan,

Moreno

et al. 2024

Preprint

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High platelet reactivity is associated with adverse clinical events and is more frequent in people with diabetes mellitus (DM). To better understand platelet dysfunction in DM, we performed a proteomic analysis in platelets from a matched cohort of 34 people without, and 42 people with type 2 DM. The cohorts were matched by clinical characteristics including age, sex, and coronary artery disease burden. Using high sensitivity unbiased proteomics, we consistently identified over 2,400 intracellular proteins, and detected proteins that are differentially released by platelets from people with diabetes in response to low dose thrombin. Importantly, we identified the endoplasmic reticulum (ER) protein SEC61 translocon subunit beta (SEC61B) was increased in platelets from humans and mice within vivohyperglycemia. SEC61B was increased in megakaryocytes in mouse models of diabetes, in association with megakaryocyte ER stress. A rise in cytosolic calcium is a key aspect in platelet activation, and the SEC61 translocon is known to act as a channel for ER calcium leak. We demonstrate that cultured cells overexpressing SEC61B have increased calcium flux and decreased protein synthesis. In accordance, hyperglycemic mouse platelets mobilized more calcium to the cytosol and had lower protein synthesis compared with normoglycemic platelets. Independently,in vitroinduction of ER stress increased platelet SEC61B expression and markers of platelet activation. We propose a mechanism whereby ER stress-induced upregulation of platelet SEC61B leads to increased cytosolic calcium, potentially contributing to platelet hyperactivity in people with diabetes.Key PointsPlatelet SEC61B is increased in hyperglycemia and contributes to increased endoplasmic reticulum (ER) calcium leakIncreased ER calcium leak is associated with ER stress and platelet hyperactivity

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“…SEC61G was found to be overexpressed in BC and might co-amplify with epidermal growth factor receptor (EGFR) ( Reis-Filho et al, 2006 ). Lu et al reported that the expression of SEC61G in BC was negatively correlated with its promoter methylation ( Lu et al, 2021 ). In our research, similar trend could be found that the expression of SEC61G was negatively related with the methylation of cg00945507.…”

Section: Discussionmentioning

confidence: 99%

A Novel Gene Prognostic Signature Based on Differential DNA Methylation in Breast Cancer

et al. 2021

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Background: DNA methylation played essential roles in regulating gene expression. The impact of DNA methylation status on the occurrence and development of cancers has been well demonstrated. However, little is known about its prognostic role in breast cancer (BC).Materials: The Illumina Human Methylation450 array (450k array) data of BC was downloaded from the UCSC xena database. Transcriptomic data of BC was downloaded from the Cancer Genome Atlas (TCGA) database. Firstly, we used univariate and multivariate Cox regression analysis to screen out independent prognostic CpGs, and then we identified methylation-associated prognosis subgroups by consensus clustering. Next, a methylation prognostic model was developed using multivariate Cox analysis and was validated with the Illumina Human Methylation27 array (27k array) dataset of BC. We then screened out differentially expressed genes (DEGs) between methylation high-risk and low-risk groups and constructed a methylation-based gene prognostic signature. Further, we validated the gene signature with three subgroups of the TCGA-BRCA dataset and an external dataset GSE146558 from the Gene Expression Omnibus (GEO) database.Results: We established a methylation prognostic signature and a methylation-based gene prognostic signature, and there was a close positive correlation between them. The gene prognostic signature involved six genes: IRF2, KCNJ11, ZDHHC9, LRP11, PCMT1, and TMEM70. We verified their expression in mRNA and protein levels in BC. Both methylation and methylation-based gene prognostic signatures showed good prognostic stratification ability. The AUC values of 3-years, 5-years overall survival (OS) were 0.737, 0.744 in the methylation signature and 0.725, 0.715 in the gene signature, respectively. In the validation groups, high-risk patients were confirmed to have poorer OS. The AUC values of 3 years were 0.757, 0.735, 0.733 in the three subgroups of TCGA dataset and 0.635 in GSE146558 dataset.Conclusion: This study revealed the DNA methylation landscape and established promising methylation and methylation-based gene prognostic signatures that could serve as potential prognostic biomarkers and therapeutic targets.

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SEC61G overexpression and DNA amplification correlates with prognosis and immune cell infiltration in head and neck squamous cell carcinoma

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 13 publications

References 35 publications

Effect of CB2 Stimulation on Gene Expression in Pediatric B-Acute Lymphoblastic Leukemia: New Possible Targets

Effect of CB2 Stimulation on Gene Expression in Pediatric B-Acute Lymphoblastic Leukemia: New Possible Targets

Identification of SEC61B as a novel regulator of calcium flux and platelet hyperreactivity in diabetes mellitus

A Novel Gene Prognostic Signature Based on Differential DNA Methylation in Breast Cancer

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