Format

Send to

Choose Destination
PLoS One. 2014 Nov 21;9(11):e110472. doi: 10.1371/journal.pone.0110472. eCollection 2014.

MicroRNA-383 regulates the apoptosis of tumor cells through targeting Gadd45g.

Author information

1
Institute of Epigenetics and Cancer Research, Medical Science Building C-315, School of Medicine, Tsinghua University, Beijing 100084, China.
2
Department of Transfusion Medicine, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
3
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, 150 Jimo Road/1239 Siping Road, Shanghai 200120/200092, China.

Abstract

BACKGROUND:

MicroRNAs (miRNAs) are a class of small non-coding single-stranded RNA molecules that inhibit gene expression at post-transcriptional level. Gadd45g (growth arrest and DNA-damage-inducible 45 gamma) is a stress-response protein, which has been implicated in several biological processes, including DNA repair, the cell cycle and cell differentiation.

RESULTS:

In this work, we found that miR-383 is a negative regulator of Gadd45g. Forced expression of miR-383 decreased the expression of Gadd45g through binding to the 3' untranslated region (3'-UTR), whereas inhibition of miR-383 increased Gadd45g expression. The presence of miR-383 increased the cellular sensitivity to DNA damage in breast cancer cells, which was rescued by ectopic expression of Gadd45g without the 3'-UTR. miR-383 also regulates the expression of Gadd45g in embryonic stem (ES) cells, but not their apoptosis under genotoxic stress. miR-383 was further showed to negatively regulate ES cell differentiation via targeting Gadd45g, which subsequently modulates the pluripotency-associated genes. Taken together, our study demonstrates that miR-383 is a negative regulator of Gadd45g in both tumor cells and ES cells, however, has distinct function in regulating cell apoptosis. miR-383 may be used as antineoplastic agents in cancer chemotherapy.

CONCLUSION:

We demonstrate for the first time that miR-383 can specifically regulates the expression of Gadd45g by directly targeting to the 3-UTR region of Gadd45g mRNA, a regulatory process conserved in human tumor cells and mouse embryonic stem cells. These two compotents can be potentially used as antineoplastic agents in cancer chemotherapy.

PMID:
25415264
PMCID:
PMC4240536
DOI:
10.1371/journal.pone.0110472
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center