Chen Dong, Guo Yihong, Chen Yaqiu, Guo Qiaonan, Chen Junyi, Li Yining, Zheng Qiuping, Jiang Minyao, Xi Ming, Cheng Lu
Department of Urology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Department of Oncological Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Cancer Med. 2020 Apr;9(8):2846-2858. doi: 10.1002/cam4.2664. Epub 2020 Feb 18.
The aim of this study was to investigate the mechanism by which growth arrest-specific transcript 5 (GAS5) regulates bladder cancer cells. Bladder cancer samples were collected and tested for experiment. Dual-luciferase reporter assay was used to verify the downstream target genes for GAS5 and miR-21. The expression level of GAS5 was decreased and that of miR-21 was increased, indicating a negative correlation between the two. Patients with high GAS5 level and low miR-21 level had relatively longer survival rates. GAS5 inhibited bladder cancer cells proliferation and promoted apoptosis, and miR-21 had the opposite effects. MiR-21 was a direct target for GAS5, whereas phosphatase and tensin homolog (PTEN) was a direct target gene of miR-21. Low expression of miR-21 could reverse the proliferative and antiapoptotic effects caused by GAS5 silencing. High levels of GAS5 and low levels of miR-21 might be associated with a higher survival rate in bladder cancer patients. GAS5 could exert antiproliferative and proapoptotic effects on bladder cancer cells through miR-21 and PTEN.
本研究的目的是探究生长停滞特异性转录本5（GAS5）调控膀胱癌细胞的机制。收集膀胱癌样本并进行实验检测。采用双荧光素酶报告基因检测法验证GAS5和miR-21的下游靶基因。GAS5表达水平降低，miR-21表达水平升高，表明二者呈负相关。GAS5水平高且miR-21水平低的患者生存率相对较长。GAS5抑制膀胱癌细胞增殖并促进凋亡，而miR-21则具有相反的作用。miR-21是GAS5的直接靶标，而磷酸酶和张力蛋白同源物（PTEN）是miR-21的直接靶基因。miR-21低表达可逆转GAS5沉默所导致的增殖和抗凋亡作用。高水平的GAS5和低水平的miR-21可能与膀胱癌患者较高的生存率相关。GAS5可通过miR-21和PTEN对膀胱癌细胞发挥抗增殖和促凋亡作用。
