Short hairpin RNA (shRNA) constructs targeting high mobility group box-1 (HMGB1) expression leads to inhibition of prostate cancer cell survival and apoptosis

被引:148
作者
Gnanasekar, Munirathinam [1 ]
Thirugnanam, Sivasakthivel [1 ]
Ramaswamy, Kalyanasundaram [1 ]
机构
[1] Univ Illinois, Coll Med, Dept Biomed Sci, Rockford, IL 61107 USA
关键词
HMGB1; LNCaP; prostate cancer; ShRNA; GLYCATION END-PRODUCTS; SMALL INTERFERING RNA; MAMMALIAN-CELLS; HIGH-MOBILITY-GROUP-BOX-1; HMGB1; CHROMATIN PROTEIN; AMPHOTERIN; INFLAMMATION; RAGE; RECEPTOR; THERAPY;
D O I
10.3892/ijo_00000166
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
High mobility group box protein I (HMGB1), transcriptional activity regulatory protein is associated with most cancers including prostate cancer. To investigate the effects of down-regulation of HMGB1 expression, we have transfected LNCaP cells with four short hairpin RNA (shRNA) targeting HMGB I plasmid vectors. Transfection with the four shRNAs efficiently and specifically reduced the HMGB1 expression in LNCaP cells. The gene silencing effects on HMGB1 expression were subsequently confirmed by RT-PCR and immunoblotting analyses. Down-regulation of HMGB1 expression resulted in the inhibition of cell growth in LNCaP prostate cancer cells and the decreased cell number was due to transfected cells undergoing apoptosis via caspase-3-dependent pathways. These findings suggest that HMGB I is critical for the survival of prostate cancer cells and targeted knockdown of HMGB1 mRNA can be used as a strategy to kill prostate cancer cells. Our findings may have some potential therapeutic relevance for treating prostate cancer.
引用
收藏
页码:425 / 431
页数:7
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