Su Xiangyu, Gao Chanchan, Feng Xiaoyao, Jiang Ming
Department of Oncology, Zhongda Hospital, The Affiliated Hospital of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
Clinical Medicine, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
Exp Ther Med. 2020 Apr;19(4):3081-3089. doi: 10.3892/etm.2020.8540. Epub 2020 Feb 21.
Esophageal squamous cell carcinoma (ESCC) is a common cancer in China and has a high mortality rate. MicroRNAs (miRs) are a family of post-transcriptional regulators, which negatively regulate target gene expression. miR-613 has been revealed to be a diagnostic and prognostic biomarker in ESCC. However, the role of miR-613 in ESCC remains unclear. In the present study, miR-613 expression was identified to be reduced in tumor tissues in comparison with corresponding adjacent normal tissues. TargetScan and a dual-luciferase reporter assay verified glucose-6-phosphate dehydrogenase (G6PD) as a direct target of miR-613. In contrast with miR-613, G6PD expression was increased in tumor tissues compared with matched healthy tissues. Furthermore, overexpression of miR-613 inhibited cell migration and invasion of Eca109 cells compared with controls, while G6PD overexpression reversed the inhibition induced by miR-613, as determined by wound healing and Transwell assays. In addition, miR-613 overexpression decreased the mRNA and protein expression of G6PD, matrix metalloproteinase (MMP)2 and MMP9, and reduced the phosphorylation of signal transducer and activator of transcription 3 (STAT3) compared with controls, while G6PD reversed the effects of miR-613. However, miR-613 and G6PD did not affect the expression of STAT3. In conclusion, the aforementioned results suggest that miR-613 targets G6PD to suppress ESCC cell migration and invasion through reduced MMP2 and MMP9 expression and inactivation of the STAT3 signaling pathway. Thus, the present study may provide a new molecular foundation for treatment of ESCC.
食管鳞状细胞癌(ESCC)是中国常见的癌症,死亡率很高。微小RNA(miR)是一类转录后调节因子,可负向调节靶基因表达。miR-613已被揭示为ESCC的一种诊断和预后生物标志物。然而,miR-613在ESCC中的作用仍不清楚。在本研究中,与相应的相邻正常组织相比,miR-613在肿瘤组织中的表达被确定降低。TargetScan和双荧光素酶报告基因检测验证了葡萄糖-6-磷酸脱氢酶(G6PD)是miR-613的直接靶标。与miR-613相反,与匹配的健康组织相比,G6PD在肿瘤组织中的表达增加。此外,通过伤口愈合和Transwell检测确定,与对照组相比,miR-613的过表达抑制了Eca109细胞的迁移和侵袭,而G6PD的过表达逆转了miR-613诱导的抑制作用。此外,与对照组相比,miR-613的过表达降低了G6PD、基质金属蛋白酶(MMP)2和MMP9的mRNA和蛋白表达,并降低了信号转导和转录激活因子3(STAT3)的磷酸化,而G6PD逆转了miR-613的作用。然而,miR-613和G6PD不影响STAT3的表达。总之,上述结果表明,miR-613靶向G6PD,通过降低MMP2和MMP9的表达以及STAT3信号通路的失活来抑制ESCC细胞的迁移和侵袭。因此,本研究可能为ESCC的治疗提供新的分子基础。