长链非编码RNA-IUR通过海绵化miR-24上调喉鳞状细胞癌中的P53
LncRNA-IUR Sponges miR-24 to Upregulate P53 in Laryngeal Squamous Cell Carcinoma.
作者信息
Wei Cen, Wei Huaqing, Wu Xun, Nong Guangyao, Wu Chenglin, Lee Jinli, Meng Ning, Yu Dahai, Su Jiping, Guo Mengzhu, Qin Jiangyuan, Fan Xuemin
机构信息
ENT & HN Surgery Department, Wuming Hospital of Guangxi Medical University, Nanning 530199, People's Republic of China.
Department of Cardiology, Wuming Hospital of Guangxi Medical University, Nanning 530199, People's Republic of China.
出版信息
Cancer Manag Res. 2020 Nov 16;12:11639-11647. doi: 10.2147/CMAR.S236188. eCollection 2020.
OBJECTIVE
The functions of lncRNA-IUR in laryngeal squamous cell carcinoma (LSCC) were investigated in this study.
METHODS
RT-qPCR and paired -test were used to measure and compare expression levels of IUR, miR-24 and p53 in LSCC and non-tumor tissues. Human LSCC cell line UM-SCC-17A was used and transfected by pcDNA3.1 vector to overexpress IUR and miR-24. The transwell assay and wound healing assay illustrated the effect of overexpression of IUR or miR-24 in the cell invasion and migration of LSCC. Subcutaneous tumor model in nude mice was carried out to demonstrate the mechanism between IUR and miR-24 in regulating tumor growth.
RESULTS
We found that IUR was downregulated in LSCC. Low expression levels of IUR were correlated with the poor survival of LSCC patients. Overexpression experiments showed that overexpression of IUR led to increased, while overexpression of miR-24 led to decreased expression levels of p53 in LSCC cells. And bioinformatics analysis showed that IUR may sponge miR-24. Cell proliferation assay showed that overexpression of IUR and p53 led to decreased proliferation rate of LSCC cells, while overexpression of miR-24 led to increased proliferation rate of LSCC cells. We also illustrated that overexpression of IUR promoted cell migration and invasion while miR-24 had opposite effects. In addition, subcutaneous tumor model in nude mice showed that overexpression of miR-24 attenuated the effects of overexpression of IUR on the expression of p53 and cancer cell proliferation.
CONCLUSION
IUR sponges miR-24 to upregulate p53 in LSCC, thereby inhibiting cancer cell proliferation.
目的
本研究旨在探究长链非编码RNA-IUR（lncRNA-IUR）在喉鳞状细胞癌（LSCC）中的作用。
方法
采用RT-qPCR和配对检验来测量和比较IUR、miR-24和p53在LSCC组织和非肿瘤组织中的表达水平。使用人LSCC细胞系UM-SCC-17A，并用pcDNA3.1载体转染以过表达IUR和miR-24。通过Transwell实验和伤口愈合实验阐述过表达IUR或miR-24对LSCC细胞侵袭和迁移的影响。建立裸鼠皮下肿瘤模型以证明IUR和miR-24在调节肿瘤生长中的机制。
结果
我们发现IUR在LSCC中表达下调。IUR低表达水平与LSCC患者的不良生存相关。过表达实验表明，过表达IUR导致LSCC细胞中p53表达水平升高，而过表达miR-24导致p53表达水平降低。生物信息学分析表明IUR可能吸附miR-24。细胞增殖实验表明，过表达IUR和p53导致LSCC细胞增殖速率降低，而过表达miR-24导致LSCC细胞增殖速率升高。我们还表明，过表达IUR促进细胞迁移和侵袭，而miR-24则有相反的作用。此外，裸鼠皮下肿瘤模型表明，过表达miR-24减弱了过表达IUR对p53表达和癌细胞增殖的影响。
结论
在LSCC中，IUR通过吸附miR-24上调p53，从而抑制癌细胞增殖。
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