Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, China.
Int J Biochem Cell Biol. 2013 Mar;45(3):645-56. doi: 10.1016/j.biocel.2012.12.002. Epub 2012 Dec 12.
Identification and functional analysis of novel potential cancer-associated genes is of great importance for developing diagnostic, preventive and therapeutic strategies for cancer treatment and management. In the present study, we isolated and identified a novel gene, proline-rich protein 11 (PRR11), implicated in both cell cycle progression and lung cancer. Our results showed that PRR11 was periodically expressed in a cell cycle-dependent manner, and RNAi-mediated silencing of PRR11 caused significant S phase arrest as well as growth retardation in HeLa cells. Moreover, PRR11 was overexpressed at both mRNA and protein levels in lung cancer tissues as compared with normal lung tissues. Large scale in silico analysis of clinical microarray datasets also indicated that high expression of PRR11 was significantly associated with poor prognosis in lung cancer patients. RNAi-mediated silencing of PRR11 caused S phase arrest, suppressed cellular proliferation, colony formation ability in lung cancer cells and inhibited tumorigenic potential in nude mice. Knockdown of PRR11 also inhibited cell migration and invasion ability in lung cancer cells. Furthermore, microarray analysis revealed that PRR11 knockdown caused the dysregulation of multiple critical pathways and various important genes involved in cell cycle, tumorigenesis and metastasis (e.g. CCNA1, RRM1, MAP4K4 and EPB41L3). Taken together, our results strongly demonstrated that this newly identified gene, PRR11, had a critical role in both cell cycle progression and tumorigenesis, and might serve as a novel potential target in the diagnosis and/or treatment of human lung cancer.
鉴定和功能分析新的潜在的癌症相关基因对于开发癌症治疗和管理的诊断、预防和治疗策略具有重要意义。在本研究中,我们分离和鉴定了一个新的基因,富含脯氨酸蛋白 11(PRR11),该基因与细胞周期进程和肺癌有关。我们的结果表明,PRR11 以细胞周期依赖性方式周期性表达,并且 RNAi 介导的 PRR11 沉默导致 HeLa 细胞中 S 期停滞和生长迟缓。此外,与正常肺组织相比,肺癌组织中 PRR11 的 mRNA 和蛋白质水平均过度表达。临床微阵列数据集的大规模计算机分析也表明,PRR11 的高表达与肺癌患者的预后不良显著相关。PRR11 的 RNAi 介导的沉默导致 S 期停滞,抑制了肺癌细胞的细胞增殖、集落形成能力,并抑制了裸鼠中的致瘤潜能。PRR11 的敲低也抑制了肺癌细胞的迁移和侵袭能力。此外,微阵列分析显示,PRR11 敲低导致多个关键途径和涉及细胞周期、肿瘤发生和转移的重要基因的失调(例如,CCNA1、RRM1、MAP4K4 和 EPB41L3)。总之,我们的研究结果强烈表明,这个新鉴定的基因 PRR11 在细胞周期进程和肿瘤发生中都具有关键作用,可能成为诊断和/或治疗人类肺癌的一个新的潜在靶点。