Wang Chunyang, Yu Liang, Ren Xianyue, Wu Tong, Chen Xijuan, Huang Yulei, Cheng Bin
Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, Guangdong 510060, P.R. China.
J Cancer. 2019 Jun 2;10(11):2541-2551. doi: 10.7150/jca.29265. eCollection 2019.
: We previously demonstrated that () gene is associated with the development and progression of tongue squamous cell carcinoma (TSCC), but the underlying mechanism is unknown. This study aimed to investigate the molecular mechanism underlying oncogenic potential of PRR11 in TSCC cells. : Overexpression and knockdown of PRR11 were performed by plasmid transfection into SCC15 and HSC3 human TSCC cells. Expressions of mRNA and protein were assessed by qRT-PCR and Western blot, respectively. Cell proliferation and invasion were determined by CCK-8 and Transwell assay, respectively. tumor growth and cell cycle were determined by a nude mice model of subcutaneous tumorigenesis and flow cytometry, respectively. : Overexpression of PRR11 significantly enhanced TSCC cells proliferation and the invasive ability of TSCC cells, whereas PRR11 knockdown in TSCC cells exhibited a reverse trend. In addition, the subcutaneous tumorigenicity assay showed that PRR11 knockdown significantly reduced tumor size and the Ki67 (a proliferation marker)expression in the tumor tissue. Flow cytometry analysis revealed that PRR11 overexpression significantly decreased the proportion of cells in S phase, whereas PRR11 knockdown in TSCC cells exhibited a reverse trend. Furthermore, PRR11 overexpression simultaneously down-regulated two cyclin-dependent kinase inhibitors (CKIs), p21 and p27 and up-regulated CDK2 and Cyclin A2 in TSCC cells. PRR11 knockdown again exhibited reverse trends of expressions of the above proteins.: These results suggested that PRR11 promoted cell proliferation by regulating the expressions of p21, p27, CDK2 and Cyclin A to facilitate S/G phase transition in TSCC cells.
我们之前证明了（）基因与舌鳞状细胞癌（TSCC）的发生和发展相关，但潜在机制尚不清楚。本研究旨在探究PRR11在TSCC细胞中致癌潜能的分子机制。：通过质粒转染将PRR11过表达和敲低导入SCC15和HSC3人TSCC细胞。分别通过qRT-PCR和蛋白质印迹法评估mRNA和蛋白质的表达。分别通过CCK-8和Transwell实验测定细胞增殖和侵袭能力。分别通过皮下成瘤裸鼠模型和流式细胞术测定肿瘤生长和细胞周期。：PRR11过表达显著增强TSCC细胞增殖及TSCC细胞的侵袭能力，而TSCC细胞中PRR11敲低则呈现相反趋势。此外，皮下成瘤实验表明，PRR11敲低显著减小肿瘤大小及肿瘤组织中增殖标志物Ki67的表达。流式细胞术分析显示，PRR11过表达显著降低S期细胞比例，而TSCC细胞中PRR11敲低则呈现相反趋势。此外，PRR11过表达同时下调TSCC细胞中两种细胞周期蛋白依赖性激酶抑制剂（CKIs）p21和p27，并上调CDK2和细胞周期蛋白A2。PRR11敲低再次呈现上述蛋白表达的相反趋势。这些结果表明，PRR11通过调节p21、p27、CDK2和细胞周期蛋白A的表达促进细胞增殖，以促进TSCC细胞的S/G期转换。
