Hu Xiao-Tong, Chen Wei, Zhang Fu-Biao, Shi Qing-Lan, Hu Jian-Bin, Geng Shu-Min, He Chao
Biomedical Research Center, Sir Run Run Shaw Hospital, Zhejiang University, Zhejiang 310016, PR China.
Oncol Rep. 2009 Nov;22(5):1247-52. doi: 10.3892/or_00000561.
Colorectal cancer is one of the most common causes of cancer-related deaths throughout the world. Recently, we reported that proteasome subunit PSMA7 located on 20q13 amplicon was overexpressed and associated with liver metastasis of colorectal cancer. The results indicate that PSMA7 may play an important role in the colorectal cancer progression and provide a unique target site for the development of therapeutic drugs. However, it is unknown how aberrant PSMA7 activation critically regulates the metastatic behavior of colorectal cancer cells. To investigate the role of PSMA7 in the progression of colorectal cancer, we employed the RNA interference technology to knock down the PSMA7 gene in human colon cancer cell line RKO and analyzed its effect and explored the involved mechanisms. Depletion of PSMA7 by shRNA in RKO cells inhibited their anchorage-independent growth and cell invasion and migration. Moreover, PSMA7 depletion was able to strongly suppress the in vivo tumorigenic ability of RKO cells. These effects may be induced by inhibiting CD44 expression directly or indirectly. Genetic or pharmacological inhibition of PSMA7 may therefore be a beneficial strategy in the treatment of colorectal cancer patients.
结直肠癌是全球癌症相关死亡的最常见原因之一。最近，我们报道位于20q13扩增子上的蛋白酶体亚基PSMA7过表达，并与结直肠癌肝转移相关。结果表明，PSMA7可能在结直肠癌进展中起重要作用，并为治疗药物的开发提供了一个独特的靶点。然而，尚不清楚异常的PSMA7激活如何关键地调节结直肠癌细胞的转移行为。为了研究PSMA7在结直肠癌进展中的作用，我们采用RNA干扰技术在人结肠癌细胞系RKO中敲低PSMA7基因，分析其作用并探索其相关机制。在RKO细胞中通过shRNA耗尽PSMA7可抑制其非锚定依赖性生长以及细胞侵袭和迁移。此外，PSMA7的耗尽能够强烈抑制RKO细胞的体内致瘤能力。这些作用可能是通过直接或间接抑制CD44表达诱导的。因此，对PSMA7进行基因或药理学抑制可能是治疗结直肠癌患者的有益策略。
