Journal
CANCER LETTERS
Volume 370, Issue 2, Pages 216-221Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2015.10.023
Keywords
Esophageal squamous cancer cell; p53; miR-34a; Senescence
Categories
Funding
- National Natural Science Foundation of China [81271584, 81372620, 81071164, 81420108018, 81527803]
- Provincial Natural Science Funds of the Zhejiang Province of China [Q15H160012]
- Main Scientific and Technological Project of the Zhejiang Province of China [2013C03044-1]
- General Project of Zhejiang Provincial Health Bureau [2015122303]
Ask authors/readers for more resources
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 MU assay demonstrated an miR-34a-related cytotoxic effect in cell growth. Senescence-associated beta-galactosidase (SA-beta-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. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available