SiRNA-Mediated Silencing of HMGA2 Induces Apoptosis and Cell Cycle Arrest in Human Colorectal Carcinoma

被引：48
作者：
Esmailzadeh S. [1 ]
Mansoori B. [1 ,2 ]
Mohammadi A. [1 ]
Shanehbandi D. [1 ]
Baradaran B. [1 ]
机构：
[1] Immunology Research Center, Tabriz University of Medical Sciences, Tabriz
[2] Student Research Committee, Tabriz University of Medical Sciences, Tabriz
来源：
Journal of Gastrointestinal Cancer | 2017年 / 48卷 / 2期
关键词：
Apoptosis; Cell cycle; Colorectal carcinoma; HMGA2 (high mobility group A2); Small interference RNA (siRNA);
D O I：
10.1007/s12029-016-9871-z
中图分类号：
学科分类号：
摘要：
Purpose: Overexpression of HMGA2, known as small non-histone chromosomal protein, is associated with progression of various tumors, including colorectal cancers. The aim of this study was to investigate the effect of a specific HMGA2 siRNA on apoptosis and cell cycle of HCT-116 (colorectal carcinoma) cells. Methods: The cells were transfected with siRNAs using a transfection reagent. The cytotoxic effects of HMGA2 siRNA on colorectal carcinoma cells were determined using MTT assay. Relative HMGA2 mRNA and protein levels were measured by QRT-PCR and western blotting, respectively. Apoptosis was measured by a TUNEL test based on labeling of DNA strand breaks. We also evaluated caspase-3, caspase-8, and caspase-9 expression by QRTPCR to determine which pathway is involved in apoptosis. Cell cycle was assessed by FACS and cell cycle analysis using PI DNA staining. Results: HMGA2 siRNA significantly reduced both mRNA and protein expression levels 48 h after transfection and dose-dependent manner in colorectal carcinoma cells. We also showed that the silencing of HMGA2 led to the induction of apoptosis through intrinsic pathway and cell cycle arrest in G2/M phases of interphase in HCT-116 cells in vitro. Conclusions: These results propose that HMGA2 might play an important role in the progression of colorectal carcinoma and might be a potential therapeutic target for trigger apoptosis and cell cycle arrest in colorectal carcinoma. © 2016, Springer Science+Business Media New York.
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页码：156 / 163
页数：7
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