Li Hongyu, Wang Shixuan, Zhu Tao, Zhou Jinhua, Xu Qian, Lu Yunping, Ma Ding
Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei 430030, PR China.
Oncol Rep. 2006 Sep;16(3):491-6.
The prolyl isomerase Pin1, which specifically catalyzes conformational changes in certain proline-directed phosphorylation sites, is thought to be a critical catalyst for multiple oncogenic pathways. However, little is known about the role of Pin1 in human cervical cancer. Our previous study showed that Pin1 was overexpressed in cervical cancer tissues as well as cell lines. In this study, whether Pin1 is involved in cervical oncogenesis by regulating cyclin D1 was explored and the potential of Pin1-targeted gene silencing in inhibiting cellular growth and tumorigenicity in cervical cancer was investigated. A Pin1-directed shRNA and a sense Pin1 plasmid were constructed, and then the effects of the shRNA and the sense plasmid on HeLa cells were evaluated. The results showed that Pin1 directly regulated cyclin D1 levels. In addition, silencing Pin1 with RNAi significantly reduced cancer cell proliferation, colony formation, and strongly enhanced the apoptosis of HeLa cells. It is suggested that Pin1 may contribute to cervical tumorigenesis by regulating cyclin D1 expression and Pin1 may serve as a promising molecular target for diagnostics and therapeutics in cervical cancer.
脯氨酰异构酶Pin1可特异性催化某些脯氨酸定向磷酸化位点的构象变化，被认为是多种致癌途径的关键催化剂。然而，关于Pin1在人类宫颈癌中的作用却知之甚少。我们之前的研究表明，Pin1在宫颈癌组织以及细胞系中均过度表达。在本研究中，我们探讨了Pin1是否通过调节细胞周期蛋白D1参与宫颈癌发生，并研究了靶向Pin1的基因沉默在抑制宫颈癌细胞生长和致瘤性方面的潜力。构建了针对Pin1的短发夹RNA（shRNA）和正义Pin1质粒，然后评估了shRNA和正义质粒对HeLa细胞的影响。结果表明，Pin1直接调节细胞周期蛋白D1的水平。此外，用RNA干扰沉默Pin1可显著降低癌细胞增殖、集落形成，并强烈增强HeLa细胞的凋亡。提示Pin1可能通过调节细胞周期蛋白D1的表达促进宫颈癌发生，且Pin1可能成为宫颈癌诊断和治疗的一个有前景的分子靶点。
