MicroRNA-34a induces a senescence-like change via the down-regulation of SIRT1 and up-regulation of p53 protein in human esophageal squamous cancer cells with a wild-type p53 gene background.

摘要: MiR-34a has been reported as a non-coding RNA universally expressed in normal old cells and probable suppressor of diverse cancer cells; however, this miRNA's expression anti-tumor mechanism esophageal squamous (ESCC) remains unclear. We explored these questions three human ESCC lines, KYSE-450, KYSE-410, ECa-109, with wild-type p53 mutant backgrounds. Through specific stem-loop RT primer for miR-34a, we examined the relevant level miR-34a cell lines using real-time reverse transcription PCR (qRT-PCR). found that induced by DNA damage agent adrmycin (ADR) was both p53- time-dependent. Following incubation cellular growth inhibition exhibited differently harbored different Furthermore, MTT assay demonstrated an miR-34a-related cytotoxic effect growth. Senescence-associated β-galactosidase (SA-β-Gal) staining used to examine senescence-like phenotypes miR-34a. Mechanistic investigation suggested down-regulation Sirtuin1 (SIRT1) up-regulation p53/p21 contributed ECa-109 cells, while neither apoptosis-related proteins PARP caspase-3 caused significant changes. In summary, our findings indicated intrinsic relatively low among backgrounds ADR treatment times. The primarily dependent on regulation SIRT1 protein, not apoptosis-associated proteins.