Project description:To investigate the function of CELF2 in non-melanoma skin cancer, we performed immunofluorescence staining studies and found lower CELF2 expression in human squamous cell carcinoma (SCC) tumors than in adjacent normal skin. CELF2 expression was also downregulated during both ultraviolet light- and chemical-induced skin tumorigenesis in mice, suggesting that CELF2 loss might promote skin cancer development. By using shRNA-mediated knockdown (KD) of CELF2 expression, we showed that CELF2 deficiency significantly increased SCC cell proliferation and colony growth in vitro and increased SCC tumor growth in a xenograft mouse model. Although control SCC cells were sensitive to anticancer drugs such as doxorubicin, CELF2-KD SCC cells were resistant to drug-induced tumor growth retardation. Through RNA-seq analysis, we identified that CELF2 loss led to activation of KRT80 and GDF15, which could confer growth and survival advantages to CELF2-deficient SCC cells.
Project description:In this study, CLIP-seq was used to identify sites of CELF2-mRNA interactions in JSL1 T cells. (SRA study SRP059226, BioProject accession PRJNA285907)
Project description:Emerging evidence suggests that homeoproteins can act as modulators of tumor initiation and progression. Our findings show that loss of DLX3 tumor suppressive function acts as a tumor promoter through regulation of ERBB2 and EGFR signaling and also support an important inhibitory role of DLX3 in skin cancer promotion and progression, that may potentially be used as a promising prognostic marker.
Project description:CELF2 is a critical regulator of alternative splicing during T cell development and during stimulation-induced T cell activation. Here we utilize RNA-seq to globally profile the functional targets of CELF2 in a monoclonal Jurkat T cell line (JSL1 cells), including transcriptome-wide splicing targets and genes regulated at other levels of mRNA processing