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HMGI-C suppressing induces P53/caspase9 axis to regulate apoptosis in breast adenocarcinoma cells.

Authors :
Mansoori B
Mohammadi A
Shirjang S
Baradaran B
Source :
Cell cycle (Georgetown, Tex.) [Cell Cycle] 2016 Oct; Vol. 15 (19), pp. 2585-2592. Date of Electronic Publication: 2016 May 31.
Publication Year :
2016

Abstract

Purpose: The HMGI-C (high mobility group protein isoform I-C) protein is a member of the high-mobility group AT-hook (HMGA) family of small non-histone chromosomal proteins that can modulate transcription of an ample number of genes. Genome-wide studies reveal upregulation of the HMGI-C gene in many human cancers, which suggests that HMGI-C might play a critical role in the progression of various tumors. However, the exact role of HMGI-C in breast adenocarcinoma has not been made clear.<br />Methods: HMGI-C mRNA expression in breast cancer samples and marginal normal tissues was characterized using qRT-PCR. The cytotoxic effects of HMGI-C siRNA on breast adenocarcinoma cells were determined using MTT assay. Relative HMGI-C mRNA and protein levels were measured by quantitative real-time PCR and western blotting, respectively. Apoptosis detection was done using TUNEL and Annexin-V/PI assays, P53, caspase 3, 9, 8 and Bcl2 proteins evaluated by protein gel blot and miR34a, Let-7a genes investigates by QRT-PCR assay. Cell cycle was analyzed by flow cytometry assay using propidium iodide DNA staining.<br />Results: An overexpression of HMGA2 was revealed with highly statistically significant differences between breast cancer samples and marginal normal tissues (P < 0.0001). HMGI-C siRNA significantly reduced both mRNA and protein expression levels in a 48-hour period after transfection and in a dose-dependent manner. We observed that the knockdown of HMGI-C led to the significant induction of apoptosis via mitochondrial pathway by inducing miR34a and cell cycle arrest in MDA-MB-468 cells in vitro.<br />Conclusions: These results propose that HMGI-C might play a critical role in the progression of breast adenocarcinoma. Here we introduced HMGI-C as a potential therapeutic target for trigger apoptosis and cell cycle arrest in human breast adenocarcinoma. Therefore HMGI-C siRNA may be an effective adjuvant in human breast adenocarcinoma.

Details

Language :
English
ISSN :
1551-4005
Volume :
15
Issue :
19
Database :
MEDLINE
Journal :
Cell cycle (Georgetown, Tex.)
Publication Type :
Academic Journal
Accession number :
27245202
Full Text :
https://doi.org/10.1080/15384101.2016.1190892