Li Wen-Bin, Feng Jie, Geng Song-Mei, Zhang Peng-Yu, Yan Xiao-Ning, Hu Gang, Zhang Cai-Qing, Shi Bing-Jun
Department of Dermatology, The Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, The West Five Road #157, Xi'an, Shaanxi, PR China.
Cell Biol Int. 2009 Apr;33(4):548-54. doi: 10.1016/j.cellbi.2009.02.005. Epub 2009 Feb 28.
HS1-associated protein X-1 (Hax-1) is a novel intracellular protein and recent studies suggested that it is an anti-apoptotic factor in different tumors. Hax-1 expression was upregulated in various metastatic tumors and cancer cell lines, including melanoma. To understand the role of Hax-1 in melanoma development and progression, we constructed Hax-1 short interfering RNA (siRNA) expression vectors to downregulate Hax-1 expression in a human melanoma A375 cell line. One of the two Hax-1 RNA interference (RNAi) constructs significantly reduced melanoma cell viability, which was due to induction of apoptosis in A375 cells. Molecularly, the induced apoptosis through downregulation of Hax-1 expression was mediated by activation of caspase-3 and poly-ADP-ribose polymerase (PARP) enzymatic activity in A375 cells. The data indicate that Hax-1 plays a role in suppression of apoptosis and promotion of melanoma cell growth, suggesting that this Hax-1 siRNA has a therapeutic indication in control of melanoma.
HS1相关蛋白X-1（Hax-1）是一种新型细胞内蛋白，最近的研究表明它是不同肿瘤中的一种抗凋亡因子。Hax-1在包括黑色素瘤在内的各种转移性肿瘤和癌细胞系中表达上调。为了了解Hax-1在黑色素瘤发生和发展中的作用，我们构建了Hax-1小干扰RNA（siRNA）表达载体，以下调人黑色素瘤A375细胞系中的Hax-1表达。两种Hax-1 RNA干扰（RNAi）构建体中的一种显著降低了黑色素瘤细胞活力，这是由于A375细胞中凋亡的诱导。在分子水平上，通过下调Hax-1表达诱导的凋亡是由A375细胞中半胱天冬酶-3和聚ADP核糖聚合酶（PARP）酶活性的激活介导的。数据表明，Hax-1在抑制凋亡和促进黑色素瘤细胞生长中起作用，提示这种Hax-1 siRNA在黑色素瘤的控制中具有治疗指征。
