Shi Zhan, Wu Ding, Tang Run, Li Xiang, Chen Renfu, Xue Song, Zhang Chengjing, Sun Xiaoqing
Department of Urology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002 Jiangsu Province, China.
J Biosci. 2016 Jun;41(2):229-36. doi: 10.1007/s12038-016-9603-3.
The high mobility group protein A2 (HMGA2) has been demonstrated as an architectural transcription factor that is associated with pathogenesis of many malignant cancers; however, its role in prostate cancer cells remains largely unknown. To explore whether HMGA2 participates in the development and progression of prostate cancer, small interfering RNA (siRNA) targeted on human HMGA2 was transfected to suppress the HMGA2 expression in prostate cancer PC3 and DU145 cells, and then the cellular biology changes after decreased the expression of HMGA2 was examined. Our results showed that knockdown of HMGA2 markedly inhibited cell proliferation; this reduced cell proliferation was due to the promotion of cell apoptosis as the Bcl-xl was decreased, whereas Bax was up-regulated. In addition, we found that HMGA2 knockdown resulted in reduction of cell migration and invasion, as well as repressed the expression of matrix metalloproteinases (MMPs) and affected the occurrence of epithelial-mesenchymal transition (EMT) in both cell types. We further found that decreased HMGA2 expression inhibited the transforming growth factor-beta (TGF-beta)/Smad signalling pathway in cancer cells. In conclusion, our data indicated that HMGA2 was associated with apoptosis, migration and invasion of prostate cancer, which might be a promising therapeutic target for prostate cancer.
高迁移率族蛋白A2（HMGA2）已被证明是一种与多种恶性肿瘤发病机制相关的结构转录因子；然而，其在前列腺癌细胞中的作用仍 largely未知。为了探究HMGA2是否参与前列腺癌的发生和发展，将靶向人HMGA2的小干扰RNA（siRNA）转染至前列腺癌PC3和DU145细胞中以抑制HMGA2表达，然后检测HMGA2表达降低后的细胞生物学变化。我们的结果表明，敲低HMGA2显著抑制细胞增殖；这种细胞增殖的减少是由于随着Bcl-xl降低、Bax上调而促进了细胞凋亡。此外，我们发现敲低HMGA2导致细胞迁移和侵袭减少，同时抑制了两种细胞类型中基质金属蛋白酶（MMPs）的表达并影响了上皮-间质转化（EMT）的发生。我们进一步发现，HMGA2表达降低抑制了癌细胞中的转化生长因子-β（TGF-β）/Smad信号通路。总之，我们的数据表明HMGA2与前列腺癌的凋亡、迁移和侵袭相关，这可能是前列腺癌一个有前景的治疗靶点。
