PRR11 is a novel gene implicated in cell cycle progression and lung cancer

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• 作者：Ying Ji^a ; ^b ; ¹ ; Mengyu Xie^a ; ^b ; ¹ ; Huan Lan^a ; ^b ; ¹ ; Ying Zhang^a ; ^b ; Yinjiang Long^a ; ^b ; Huali Weng^a ; ^b ; Dan Li^b ; ^c ; Wei Cai^a ; ^b ; Huifang Zhu^a ; ^b ; Yulong Niu^b ; Zhengmei Yang^b ; ^d ; Chundong Zhang^a ; ^b ; Fangzhou Song^a ; ^b ; Youquan Bu^a ; ^b ; ^{buyqcn@yahoo.com.cn}
• 关键词：PRR11 ; Cancer gene ; Lung cancer ; Cell cycle ; Proliferation
• 刊名：The International Journal of Biochemistry and Cell Biology
• 出版年：2013
• 出版时间：March, 2013
• 年：2013
• 卷：45
• 期：3
• 页码：645-656
• 全文大小：3191 K

文摘

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.