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RNA Binding Protein CELF6 Modulates Expression and Alternative Splicing of Genes associated with Tumorigenesis in Non-small Cell Lung Cancer Cells.

ABSTRACT: CELF6 (CUGBP Elav-Like Family Member 6), a typical RNA binding protein, can regulate alternative splicing of pre-mRNAs, and may also participate in mRNA editing and translation. As a tumor suppressor, CELF6 is abnormally low expressed in colon cancer, breast cancer and other tumors, and is closely related to proliferation, invasion, and migration. Recent studies have shown that CELF6 has abnormally low expression in lung cancer tissues, and is increased after ultra-hypoxia treatment in A549 cells, however, the functions and molecular mechanisms of CELF6 in lung cancer are still unclear. We overexpressed CELF6 in human non-small cell lung cancer cells (A549), and set up a control; after collecting cells, we used RNA sequencing to screen for genes with significant differential expression (DEGs) after CELF6 overexpression, and significantly alternative splicing events (ASEs). CELF6 overexpression widely regulates the expression of related genes in immune response，Inflammation response, Innate immune response，TNF signaling pathway, cell adhesion molecules (CAMs) and so on. We found that CELF6 can inhibit the expression many immune-related genes, such as TNFSF10、CCL5、JUNB、BIRC3、MLKL、PIK3R2、CCL20、STAT1、MYD88 and CFS1，which mainly function in promoting tumorigenesis in lung cancer. These DEGs were validated by reverse transcriptase quantitative polymerase chain reaction (RT-PCR). In addition, CELF6 regulates the alternative splicing of a large number of genes which were enriched in p53 signaling pathway and apoptosis，such as TP53 and CD44. This study is the first to analyze the transcriptome analysis of differential gene expression and alternative splicing of CELF6 overexpression. which will provide a new idea for the gene regulation mechanism mediated by CELF6 in the production and development of NSCLC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE185865 | GEO | 2022/07/11

REPOSITORIES: GEO

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RNA Binding Protein CELF6 Modulates Expression and Alternative Splicing of Genes associated with Tumorigenesis in Non-small Cell Lung Cancer Cells.

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