Dataset Information

Small Nuclear Ribonucleoprotein Polypeptide N Accelerates Malignant Progression and Poor Prognosis in Colorectal Cancer Transcriptionally Regulated by E2F8.

ABSTRACT: Colorectal cancer is a major cause of death worldwide, and the identification of new diagnostic and prognostic biomarkers is crucial to develop new strategies to avoid colorectal cancer-related deaths. Small nuclear ribonucleoprotein polypeptide N (SNRPN) is an imprinted gene that plays an important role in various neurodevelopmental disabilities. In this study, SNRPN was highly expressed in colorectal cancer tissues and involved in the progression of this disease. Immunohistochemistry analysis of 1,310 colorectal cancer tissue samples showed that SNRPN highly expressed in cancer tissues than in adjacent tissues and was mainly localized in the nucleus. Clinical pathological factor analysis demonstrated that higher expression of SNRPN was significantly associated with larger tumor size, location of the tumor on the left-sided colon, neural invasion, and distant metastasis. Univariate and multivariate analyses showed that SNRPN expression was an independent risk factor for survival, with high expression levels indicating worse overall survival. Both in vitro and in vivo experiments confirmed that high expression of SNRPN was associated with tumor proliferation, cell cycle, and metastasis. Knocking down SNRPN blocked the cell cycle at the G2/M phase transition and promoted tumor cell apoptosis, inhibiting the progression of colorectal cancer. To explore the up-steam of SNRPN, we found by luciferase reporter assay and chromosomal immunoprecipitation assay that E2F8 was a transcriptional regulator up-steam of SNRPN in colorectal cancer. Systematic studies of SNRPN will help us discover new regulatory molecules and provide a theoretical basis for finding new molecular targets for this disease.

SUBMITTER: Ji M

PROVIDER: S-EPMC7669248 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Small Nuclear Ribonucleoprotein Polypeptide N Accelerates Malignant Progression and Poor Prognosis in Colorectal Cancer Transcriptionally Regulated by E2F8.

Ji Meiling M Ren Li L Lv Yang Y Lao Xinyuan X Feng Qingyang Q Tang Wentao W Zhuang Aobo A Liu Tianyu T Zheng Peng P Xu Jianmin J

Frontiers in oncology 20201102

Colorectal cancer is a major cause of death worldwide, and the identification of new diagnostic and prognostic biomarkers is crucial to develop new strategies to avoid colorectal cancer-related deaths. Small nuclear ribonucleoprotein polypeptide N (SNRPN) is an imprinted gene that plays an important role in various neurodevelopmental disabilities. In this study, SNRPN was highly expressed in colorectal cancer tissues and involved in the progression of this disease. Immunohistochemistry analysis ...[more]

PMID: 33224876

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Project description:BackgroundElevated Small Nuclear Ribonucleoprotein Polypeptide A (SNRPA) can enhance tumor cell growth and proliferation in various cancers. However, rarely studies focus on the comprehensive analysis of SNRPA in hepatocellular carcinoma (HCC).MethodsTCGA and GEO databases were used to analyze the mRNA expression of SNRPA in HCC. Protein expression of SNAPA was validated using immunohistochemistry. Stably transfected HCC cells were used to investigate the role of SNRPA in the progression of HCC. The functional enrichment analysis was utilized for the biological function prediction. The CIBERSORT and ssGSEA algorithms were used to evaluate the composition of the tumor microenvironment and immunocyte infiltration ratio.ResultsThe SNRPA expression was upregulated in HCC and positively correlated with tumor stage and grade. SNRPA overexpression were independent risk factors for poor overall survival (OS) and recurrence-free survival (RFS). In patients with early-stage disease, low alpha-fetoprotein expression, and better differentiation, SNRPA still exhibited the excellent prognostic value. Knockdown of SNRPA inhibited the proliferation and migration while promoting the apoptosis of HCC cells. Higher methylation of the CpG site cg16596691 correlated with longer OS in HCC patients. Genes co-expressed with SNRPA were overexpressed in HCC and correlated with shorter OS. The GO and KEGG enrichment analysis showed that SNRPA expression was related to mRNA splicing, spliceosome signaling. GSEA demonstrated that the main enrichment pathway of SNRPA-related differential genes was spliceosome signaling, cell cycle signaling, P53 signaling pathway, T cell receptor signaling pathway, natural killer cell-mediated signaling. CIBERSORT and ssGSEA algorithm revealed that SNRPA was mainly associated with the higher proportion of CD8+T cells, T cells follicular helper, T cells regulatory, Macrophages M0, and the lower proportion of T cells CD4 memory resting, NK cells resting, Monocytes, and Mast cells resting.ConclusionElevated SNRPA enhances tumor cell proliferation and correlated with poor prognosis and immune infiltrates in patients with HCC.

Project description:BackgroundLung adenocarcinoma (LUAD), as the most common histological subtype of lung cancer, is a high-grade malignancy and a leading cause of cancer-related death globally. Identification of biomarkers with prognostic value is of great significance for the diagnosis and treatment of LUAD. Heterogeneous nuclear ribonucleoprotein C (HNRNPC) is an RNA-binding protein "reader" of N6-methyladenosine (m6A) methylation, and is related to the progression of various cancers; however, its role in LUAD is unclear. The aims of this study aims were to study the expression and prognostic value of HNRNPC in LUAD.MethodsThe Oncomine database and gene expression profiling interactive analysis (GEPIA) were used for preliminary exploration of HNRNPC expression and prognostic value in LUAD. LUAD cases from The Cancer Genome Atlas (TCGA) (n = 416) and the Kaplan-Meier plotter database (n = 720) were extracted to study the differential expression and prognostic value of HNRNPC. HNRNPC expression in the National Cancer Center of China (NCC) cohort was analyzed by immunohistochemical staining, and the relationship between HNRNPC expression and survival rate evaluated using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. Several pathways that were significantly enriched in the HNRNPC high expression group were identified by Gene Set Enrichment Analysis (GSEA).ResultsFive data sets from the Oncomine and GEPIA databases all supported that HNRNPC expression is significantly higher in LUAD than in normal lung tissue. In TCGA cohort, HNRNPC was highly expressed in LUAD tissues and significantly related to age, sex, smoking history, ethnicity, lymph node metastasis, and TNM staging (P < 0.001). High HNRNPC expression was significantly correlated with poor prognosis in the three cohorts (NCC, TCGA, and K-M plotter) (P < 0.05). Multivariate Cox regression analysis showed that HNRNPC expression was an independent prognostic factor in both TCGA and NCC cohorts (P < 0.05). Further, 10 significantly enriched pathways were identified from TCGA data and 118 lung cancer cell lines in CCLE, respectively.ConclusionsHigh HNRNPC expression is significantly related to poor overall survival in patients with LUAD, suggesting that HNRNPC may be a cancer-promoting factor and a potential prognostic biomarker in LUAD.

Project description:ObjectiveTo detect the expression level of organic anion-transporting polypeptide 1B3 (OATP1B3) in hepatocellular carcinoma (HCC) and to determine the relationship between OATP1B3 expression, clinicopathological features, and prognosis.MethodsImmunohistochemical (IHC) staining was performed to detect the expression of OATP1B3 in 131 HCC specimens and in 89 adjacent nontumorous tissues. Moreover, the expression levels of OATP1B3 in 30 pairs of tumor and matched adjacent nontumorous tissues were detected by quantitative real-time polymerase chain reaction, and 34 pairs of tumor and matched adjacent nontumorous tissues were detected by Western blotting. The χ2 test was applied to analyze the correlation between OATP1B3 expression and the clinical parameters of HCC patients. The prognostic value of OATP1B3 in HCC patients was estimated by Kaplan-Meier survival analysis and the Cox stepwise proportional hazards model.ResultsCompared with that in adjacent nontumorous tissues (25.8%, 23/89), OATP1B3 expression was significantly downregulated in tumor tissues (59.5%, 78/131) (P < 0.0001). Moreover, OATP1B3 expression was markedly correlated with tumor size, recurrence, tumor differentiation, and tumor node metastasis (TNM) stage (P < 0.05 for each). However, age, sex, tumor capsule status, HBsAg, cirrhosis, tumor number, vascular invasion, and serum alpha fetoprotein were not associated with OATP1B3 expression. The overall survival (OS) and disease-free survival (DFS) of HCC patients who had high expression of OATP1B3 were significantly longer than those of patients with low expression (33.0% vs 12.9%, P = 0.001; 18.8% vs 5.3%, P < 0.0001). Cox multivariate analysis showed that OATP1B3, invasion, and TNM stage (P < 0.05 for each) were independent prognostic factors of OS in HCC patients and that OATP1B3 and TNM stage (both P < 0.05) were independent prognostic factors of DFS in HCC patients.ConclusionsThe expression of OATP1B3 in HCC patients was significantly lower than that in adjacent nontumorous tissues. OATP1B3 expression may be a potential prognostic marker in HCC patients.

Dataset Information

Small Nuclear Ribonucleoprotein Polypeptide N Accelerates Malignant Progression and Poor Prognosis in Colorectal Cancer Transcriptionally Regulated by E2F8.

Publications

Small Nuclear Ribonucleoprotein Polypeptide N Accelerates Malignant Progression and Poor Prognosis in Colorectal Cancer Transcriptionally Regulated by E2F8.

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