Open AccessIdentification and validation of critical alternative splicing events and splicing factors in gastric cancer progression
Author(s) -
Feng Haoran,
Jin Zhijian,
Liu Kun,
Peng Yi,
Jiang Songyao,
Wang Changgang,
Hu Jiele,
Shen Xiaoyun,
Qiu Weihua,
Cheng Xi,
Zhao Ren
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15835
Subject(s) - spliceosome , rna splicing , biology , gene , alternative splicing , exon , gene expression , kegg , computational biology , pi3k/akt/mtor pathway , genetics , bioinformatics , transcriptome , signal transduction , rna
Abstract Gene expression and alternative splicing (AS) interact in complex ways to regulate biological process which is associated with cancer development. Here, by integrated analysis of gene expression and AS events, we aimed to identify the hub AS events and splicing factors relevant in gastric cancer development (GC). RNA‐seq data, clinical data and AS events of 348 GC samples were obtained from the TCGA and TCGASpliceSeq databases. Cox univariable and multivariable analyses, KEGG and GO pathway analyses were performed to identify hub AS events and splicing factor/spliceosome genes, which were further validated in 53 GCs. By bioinformatics methods, we found that gene AS event‐ and gene expression‐mediated GC progression shared the same mechanisms, such as PI3K/AKT pathway, but the involved genes were different. Though expression of 17 hub AS events were confirmed in 53 GC tissues, only 10 AS events in seven genes were identified as critical candidates related to GC progression, notably the AS events (Exon Skip) in CLSTN1 and SEC16A. Expression of these AS events in GC correlated with activation of the PI3K/AKT pathway. Genes with AS events associated with clinical parameters and prognosis were different from the genes whose mRNA levels were related to clinical parameters and prognosis. Besides, we further revealed that QKI and NOVA1 were the crucial splicing factors regulating expression of AS events in GC, but not spliceosome genes. Our integrated analysis revealed hub AS events in GC development, which might be the potential therapeutic targets for GC.