Transcriptional and Post-Transcriptional Mechanisms for Oncogenic Overexpression of Ether À Go-Go K+ Channel

摘要: The human ether-a-go-go-1 (h-eag1) K(+) channel is expressed in a variety of cell lines derived from malignant tumors and clinical samples several different cancers, but otherwise absent normal tissues. It was found to be necessary for cycle progression tumorigenesis. Specific inhibition h-eag1 expression leads tumor proliferation. We report here that controlled by the p53-miR-34-E2F1 pathway through negative feed-forward mechanism. first established E2F1 as transactivator gene characterizing its promoter region. then revealed miR-34, known transcriptional target p53, an important regulator dual mechanisms directly repressing at post-transcriptional level indirectly silencing via E2F1. There strong inverse relationship between levels miR-34 protein. H-eag1antisense antagonized growth-stimulating effects upregulation SHSY5Y cells, induced knockdown overexpression, or p53 activity. Therefore, negatively regulates mechanism pathway. Inactivation activity, case many can thus cause oncogenic overexpression relieving regulation. These findings not only help us understand molecular tumorigenesis also uncover cell-cycle regulation p53-miR-34-E2F1-h-eag1 Moreover, these place with h-eag terminal effecter component (and E2F1) linker h-eag1. Our study therefore fills gap cellular function mediated