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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.
- Source :
-
Cancer Letters . Jan2016, Vol. 370 Issue 2, p216-221. 6p. - Publication Year :
- 2016
-
Abstract
- MiR-34a has been reported as a non-coding RNA universally expressed in normal old cells and a probable suppressor of diverse cancer cells; however, this miRNA's expression and anti-tumor mechanism in esophageal squamous cancer cells (ESCC) remains unclear. We explored these questions in three human ESCC lines, KYSE-450, KYSE-410, and ECa-109, with wild-type p53 and mutant p53 backgrounds. Through a specific stem-loop RT primer for miR-34a, we examined the relevant expression level of miR-34a in these three cell lines using real-time reverse transcription PCR (qRT-PCR). We found that the expression level of miR-34a induced by the DNA damage agent adrmycin (ADR) was both p53- and time-dependent. Following incubation with miR-34a, cellular growth inhibition was exhibited differently in the three cell lines harbored with different p53 backgrounds. Furthermore, the MTT assay demonstrated an miR-34a-related cytotoxic effect in cell growth. Senescence-associated β-galactosidase (SA-β-Gal) staining was used to examine senescence-like phenotypes induced by miR-34a. Mechanistic investigation suggested that the down-regulation of Sirtuin1 (SIRT1) and up-regulation of p53/p21 contributed to the anti-tumor mechanism of miR-34a in wild-type p53 ECa-109 cells, while neither of the apoptosis-related proteins PARP and caspase-3 caused significant changes. In summary, our findings indicated that the intrinsic expression of miR-34a was relatively low and was expressed differently among different p53 backgrounds and ADR treatment times. The anti-tumor effect of miR-34a was primarily dependent on the regulation of SIRT1 and p53/p21 protein, not apoptosis-associated proteins. [ABSTRACT FROM AUTHOR]
- Subjects :
- *MICRORNA
*DOWNREGULATION
*TREATMENT of esophageal cancer
*TUMOR proteins
*REVERSE transcriptase polymerase chain reaction
*GENE expression
*P53 protein
*CANCER cells
*RNA physiology
*APOPTOSIS
*BIOCHEMISTRY
*CELL lines
*CELL physiology
*CELLULAR aging
*DOXORUBICIN
*ESOPHAGEAL tumors
*GENES
*PHENOMENOLOGY
*ONCOGENES
*PROTEINS
*SQUAMOUS cell carcinoma
*TRANSFERASES
*PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 03043835
- Volume :
- 370
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Cancer Letters
- Publication Type :
- Academic Journal
- Accession number :
- 111486021
- Full Text :
- https://doi.org/10.1016/j.canlet.2015.10.023