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Title: Comprehensive Analysis of Recurrence-Associated Small Non-Coding RNAs in Esophageal Cancer [clinical study, Illumina]      
keywords:
Transcriptome or Gene expression
ID:
PRJNA276271
description:
Targeted cancer therapy for squamous cell carcinoma (SCC) has made little progress largely due to a lack of knowledge of the driving genomic alterations. Small non-coding RNAs (sncRNAs) as a potential biomarker and therapeutic target to SCC remain a challenge. We analyzed sncRNAs microarray in 108 fresh frozen specimens of esophageal squamous cell carcinoma (ESCC) as discovery set and assessed associations between sncRNAs and recurrence-free survival. SncRNA signature identified was externally validated in two independent cohorts. We investigated the functional consequences of sncRNA identified and its integrative analysis of complex cancer genomics. We identified 3 recurrence-associated sncRNAs (miR-223, miR-1269a and nc886) from discovery set and proved risk prediction model externally in high and low volume centers. We uncovered through in vitro experiment that nc886 was down-regulated by hypermethylation of its promoter region and influences splicing of pre-mRNAs with minor introns by regulating expression of minor spliceosomal small nuclear RNAs (snRNAs) such as RNU4atac. Integrative analysis from lung SCC data in The Cancer Genome Atlas revealed that patients with lower expression of nc886 had more genetic alterations of TP53, DNA damage response and cell cycle genes. nc886 inhibits minor splicing to suppress expression of certain oncogenes such as PARP1 and E2F family containing minor introns. We present risk prediction model with sncRNAs for ESCC. Among them, nc886 may contribute to complete minor splicing via regulation of minor spliceosomal snRNAs supporting the notion that aberrant alteration in minor splicing might be a key driver of ESCC. Overall design: Clinical study ESCC tumor samples.
accesstypes:
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA276271
authentication:
none
authorization:
none
ID:
pmid:27507904
name:
Homo sapiens
ncbiID:
ncbitax:9606
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject
  • P30 CA016672/CA/NCI NIH HHS/United States

  • CDP 12-187/HX/HSRD VA/United States

  • R01 CA150229/CA/NCI NIH HHS/United States

  • P30 CA125123/CA/NCI NIH HHS/United States

  • P30 AI036211/AI/NIAID NIH HHS/United States

  • S10 RR024574/RR/NCRR NIH HHS/United States

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