TY - JOUR
T1 - Regulation of HMGA1 expression by MicroRNA-296 affects prostate cancer growth and invasion
AU - Wei, Jian Jun
AU - Wu, Xinyu
AU - Peng, Yi
AU - Shi, Guizhi
AU - Olca, Basturk
AU - Yang, Ximing
AU - Daniels, Garrett
AU - Osman, Iman
AU - Ouyang, Jiangyong
AU - Hernando, Eva
AU - Pellicer, Angel
AU - Rhim, Johng S.
AU - Melamed, Jonathan
AU - Lee, Peng
PY - 2011/3/15
Y1 - 2011/3/15
N2 - Purpose: High-motility group AT-hook gene 1 (HMGA1) is a non-histone nuclear binding protein that is developmentally regulated. HMGA1 is significantly overexpressed in and associated with high grade and advance stage of prostate cancer (PC). The oncogenic role of HMGA1 is at least mediated through chromosomal instability and structural aberrations. However, regulation of HMGA1 expression is not well understood. Identification of microRNA-mediated HMGA1 regulation will provide a promising therapeutic target in treating PC. Experimental Design: In this study, we examined the functional relation between miR-296 and HMGA1 expression in several PC cell lines and a large PC cohort. We further examined the oncogenic property of HMGA1 regulated by miR-296. Results: Here we report that miR-296, a microRNA predicted to target HMGA1, specifically represses HMGA1 expression by promoting degradation and inhibiting HMGA1translation. Repression of HMGA1 by miR-296 is direct and sequence specific. Importantly, ectopic miR-296 expression significantly reduced PC cell proliferation and invasion, in part through the downregulation of HMGA1. Examining PC patient samples, we found an inverse correlation between HMGA1 and miR-296 expression: high levels of HMGA1 were associated with low miR-296 expression and strongly linked to more advanced tumor grade and stage. Conclusions: Our results indicate that miR-296 regulates HMGA1 expression and is associated with PC growth and invasion.
AB - Purpose: High-motility group AT-hook gene 1 (HMGA1) is a non-histone nuclear binding protein that is developmentally regulated. HMGA1 is significantly overexpressed in and associated with high grade and advance stage of prostate cancer (PC). The oncogenic role of HMGA1 is at least mediated through chromosomal instability and structural aberrations. However, regulation of HMGA1 expression is not well understood. Identification of microRNA-mediated HMGA1 regulation will provide a promising therapeutic target in treating PC. Experimental Design: In this study, we examined the functional relation between miR-296 and HMGA1 expression in several PC cell lines and a large PC cohort. We further examined the oncogenic property of HMGA1 regulated by miR-296. Results: Here we report that miR-296, a microRNA predicted to target HMGA1, specifically represses HMGA1 expression by promoting degradation and inhibiting HMGA1translation. Repression of HMGA1 by miR-296 is direct and sequence specific. Importantly, ectopic miR-296 expression significantly reduced PC cell proliferation and invasion, in part through the downregulation of HMGA1. Examining PC patient samples, we found an inverse correlation between HMGA1 and miR-296 expression: high levels of HMGA1 were associated with low miR-296 expression and strongly linked to more advanced tumor grade and stage. Conclusions: Our results indicate that miR-296 regulates HMGA1 expression and is associated with PC growth and invasion.
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U2 - 10.1158/1078-0432.CCR-10-0993
DO - 10.1158/1078-0432.CCR-10-0993
M3 - Article
C2 - 21138859
SN - 1078-0432
VL - 17
SP - 1297
EP - 1305
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 6
ER -
