title: HMGI-C suppressing induces P53/caspase9 axis to regulate apoptosis in breast adenocarcinoma cells.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  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.
  
  
  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.
authors.affiliation: a Immunology Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.|b Student Research Committee, Tabriz University of Medical Sciences , Tabriz , Iran.|c Aras International Branch of Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Behzad
authors.initials: B
authors.lastname: Mansoori
authors.affiliation: a Immunology Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Mohammadi
authors.affiliation: a Immunology Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Solmaz
authors.initials: S
authors.lastname: Shirjang
authors.affiliation: a Immunology Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Behzad
authors.initials: B
authors.lastname: Baradaran
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D053453:Caspase 9 / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D025743:HMGA2 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D025743:HMGA2 Protein; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D053453:Caspase 9
keywords: HMGI-C (High mobility group protein isoform I-C); P53; apoptosis; breast adenocarcinoma; caspase 9; miR-34a; small interference RNA (siRNA)