NSUN6 is a prognostic indicator and therapeutic target in esophageal squamous cell carcinoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE242287 | GEO | 2024/03/20
REPOSITORIES: GEO
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Project description:Methylation is the most common internal modification in mRNA. While the highly abundant N6-methyladonsine (m6A) modification affects most aspects of mRNA function, the precise functions of the rarer 5-methylcytosine (m5C) remains largely unknown. Here, we map m5C in the human transcriptome using methylation-dependent individual-nucleotide resolution cross-linking and immunoprecipitation (miCLIP) combined with RNA bisulfite sequencing. We identify NSUN6 as a methyltransferase with strong substrate specificity towards mRNA. NSUN6 primarily targeted three prime untranslated regions (3’UTR) at the consensus sequence motif CTCCA. Knockout and rescue experiments revealed that only mRNA methylation sites containing the consensus motif depended on the presence of NSUN6. Furthermore, ribosome profiling demonstrated that NSUN6-specific consensus motifs marked translation termination. However, even though NSUN6-methylated mRNAs were reduced in NSUN6 knockout cells, NSUN6 was dispensable for mouse embryonic development. Thus, our study identifies NSUN6 as methyltransferase targeting mRNA in a sequence- and structure-specific manner.
2020-11-20 | GSE140997 | GEO
Project description:Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignant tumors and there is a lack of biomarkers for ESCC diagnosis and prognosis. Family subunits of cholinergic nicotinic receptor genes (CHRNs) are involved in smoking behavior and tumor cell proliferation. Previous researches have shown similar molecular features and pathogenic mechanisms among ESCC, head and neck squamous cell carcinoma (HNSC), and lung squamous cell carcinoma (LUSC). Using edgeR, three mutual differentially expressed genes of CHRNs were found to be significantly upregulated at the mRNA level in ESCC, LUSC, and HNSC compared to matched normal tissues. Kaplan-Meier survival analysis showed that high expression of CHRNB4 was associated with unfavorable prognosis in ESCC and HNSC. The specific expression analysis revealed that CHRNB4 is highly expressed selectively in squamous cell carcinomas compared to adenocarcinoma. Cox proportional hazards regression analysis was performed to find that just the single gene CHRNB4 has enough independent prognostic ability, with the area under curve surpassing the tumor-node-metastasis (TNM) staging-based model, the most commonly used model in clinical application in ESCC. In addition, an effective prognostic nomogram was established combining the TNM stage, gender of patients, and expression of CHRNB4 for ESCC patients, revealing an excellent prognostic ability when compared to the model of CHRNB4 alone or TNM. Gene Set Enrichment Analysis results suggested that the expression of CHRNB4 was associated with cancer-related pathways, such as the mTOR pathway. Cell Counting Kit-8, cloning formation assay, and western blot proved that CHRNB4 knockdown can inhibit the proliferation of ESCC cells via the Akt/mTOR and ERK1/2/mTOR pathways, which might facilitate the prolonged survival of patients. Furthermore, we conducted structure-based molecular docking, and potential modulators against CHRNB4 were screened from FDA approved drugs. These findings suggested that CHRNB4 specifically expressed in SCCs, and may serve as a promising biomarker for diagnosis and prognosis prediction, and it can even become a therapeutic target of ESCC patients.
| S-EPMC7701245 | biostudies-literature
Project description:we constructed Nsun6-KO mouse, and observed that the wight and appearance of KO mice didn’t show abnormality. Through Bisulfite sequencing (BS-seq) in wild-type (WT) as well as KO mice and mRNA-seq, we identified high confident Nsun6-dependent m5C sites and performed the transcriptome analysis across five tissues.
2022-06-16 | GSE200952 | GEO
Project description:we constructed Nsun6-KO mouse, and observed that the wight and appearance of KO mice didn’t show abnormality. Through Bisulfite sequencing (BS-seq) in wild-type (WT) as well as KO mice and mRNA-seq, we identified high confident Nsun6-dependent m5C sites and performed the transcriptome analysis across five tissues.
2022-06-16 | GSE200951 | GEO
Project description:RNA expression in NSUN6 knockout cells
| PRJNA648960 | ENA
Project description:Purpose: Ubiquitin-like with plant homeodomain and ring-finger domains 1 (UHRF1) plays an essential role in DNA methylation, and the overexpression of UHRF1 is associated with poor prognosis in various cancers. Esophageal squamous cell carcinoma (ESCC) accounts for approximately 90% of esophageal cancer cases in China, but the five-year survival rate for patients is less than 10% due to limited clinical approaches for early diagnosis and treatment. The present research aimed to investigate the expression of UHRF1 in ESCC and its biological role in ESCC development. Methods: UHRF1 expression in ESCC and normal esophageal tissues was examined using immunohistochemical staining, followed by analysis of the correlation between UHRF1 expression and clinical features. In addition, the effects of lentivirus-mediated RNA interference of UHRF1 on global DNA methylation, cell proliferation, cell cycle progression and apoptosis and were investigated in ESCC cells. Results: UHRF1 was overexpressed in ESCC tissues and was an independent prognostic factor for ESCC patients. In ESCC cells, knockdown of UHRF1 caused global DNA hypomethylation, inhibited cell proliferation and induced apoptosis. Furthermore, UHRF1 depletion induced cell cycle arrest at the G2/M phase, accompanied by activation of Wee1 and DNA damage response pathway. Conclusions: Our findings identify UHRF1 as a promising prognostic marker for ESCC and suggest that UHRF1 may be a potential therapy target for ESCC patients with elevated UHRF1 expression.
| S-EPMC5706005 | biostudies-literature
Project description:Predictive value of preoperative endoscopic characteristic of esophageal tumor has not been fully evaluated. The aim of this study is to investigate the impact of esophageal luminal stenosis on survival for patients with resectable esophageal squamous cell carcinoma (ESCC).The clinicopathologic characteristics of 623 ESCC patients who underwent curative resection as the primary treatment between January 2005 and April 2009 were retrospectively reviewed. The esophageal luminal stenosis measured by endoscopy was defined as a uniform measurement preoperatively. The impact of esophageal luminal stenosis on patients' overall survival (OS) and relation with other clinicopathological features were assessed. A Cox regression model was used to identify prognostic factors.The results showed that OS significantly decreased in patients with manifest stenotic tumor compared with patients without luminal obstruction (P<0.05). Considerable esophageal luminal stenosis was associated with a higher T stage, longer tumor length, and poorer differentiation (all P<0.05). In multivariate survival analysis, esophageal luminal stenosis remained as an independent prognostic factor for OS (P= 0.036).Esophageal luminal stenosis could have a significant impact on the OS in patients with resected ESCC and may provide additional prognostic value to the current staging system before any cancer-specific treatment.
| S-EPMC5522155 | biostudies-other
Project description:Esophageal cancer is one of the most serious health problems globally because of its high incidence and mortality rate. Cisplatin (CDDP) is the primary treatment but limited by the drug resistance. However, the mechanism of cisplatin resistance remains unclear. Herein, the CDDP-resistant cell line TE-1/CDDP was established to compared with TE-1, the expression profiles of circRNAs mRNA and lncRNA were compared between TE-1/CDDP and TE-1 using microarray analysis, and used this as a basis for exploring possible mechanisms of drug resistance in genes such as HDAC9.
2023-09-14 | GSE242834 | GEO
Project description:AimsTo evaluate PIK3CA gene mutations and PIK3CA expression status in Chinese esophageal squamous cell carcinoma (ESCC) patients, and their correlation with clinicopathological characteristics and clinical outcomes.MethodsDirect sequencing was applied to investigate mutations in exons 9 and 20 of PIK3CA in 406 Chinese ESCC patients. PIK3CA expression was evaluated using immunohistochemistry analysis. The associations of PIK3CA gene mutations and PIK3CA expression with clinicopathological characteristics and clinical outcome were examined.ResultsThirty somatic point mutations (30/406, 7.4%) were identified in exon 9 whereas no mutations were detected in exon 20. PIK3CA mutations were not correlated with clinicopathological characteristics or clinical outcomes. However in the ESCC patients with family cancer history, PIK3CA mutations were independently correlated with worse overall survival (multivariate hazard ratio (HR)?=?10.493, 95% CI: 2.432-45.267, P?=?0.002). Compared to normal esophageal tissue, PIK3CA was significantly overexpressed in cancer tissue (P<0.001). PIK3CA overexpression was independently associated with higher risk of local recurrence (multivariate HR ?=?1.435, 95% CI: 1.040-1.979, P?=?0.028). In female ESCC patients, PIK3CA overexpression was independently correlated with worse overall survival (multivariate HR ?=?2.341, 95% CI: 1.073-5.108, P?=?0.033).ConclusionsOur results suggest PIK3CA gene mutation and overexpression could act as biomarkers for individualized molecular targeted therapy for Chinese ESCC patients.
| S-EPMC4108430 | biostudies-literature
Project description: Not available
| S-EPMC8585941 | biostudies-literature