[The myeloid cell leukemia-1 mRNA splicing mediated by epithelial splicing regulatory protein 1 (ESRP1) in glioma U251 cell lines]

To investigate the regulatory mechanism of myeloid cell leukemia-1 (MCL1) mRNA splicing mediated by epithelial splicing regulatory protein 1 (ESRP1) in glioma U251 cell lines.Data mining was performed in glioma patient database to find out the key sites from MCL1 sequencing results. Exogenous ESRP1 was over-expressed in U251 cells via pcDNA-ESRP1 vector. The levels of different MCL1 isoforms were detected by reverse transcription PCR and Western blotting.The mRNA and protein level of endogenous ESRP1 was lower in U251 cells than in normal gliocytes. The level of MCL1 isoform 1 was higher, while isoform 2 and 3 were lower in U251 cells than in normal gliocytes. Furthermore, MCL1 isoform 1 was reduced and isoform 3 was up-regulated in U251 cells after ESRP1 over-expression. Isoform 2 was unchanged obviously. Finally, MCL1 with the deletion of 801G and 802A sites could not be correctly spliced by ESRP1 and no significant difference was seen in the expressions of isoform 1 and 3 in mutant MCL1.Repression of ESRP1 expression or mutation in its RNA recognized sites in tumor results in the abnormality of transcript splicing of oncogenes.