Fang Xinhui, Bai Yangqiu, Zhang Lida, Ding Songze
Department of Gastroenterology and Hepatology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan 450003, P.R. China.
Oncol Lett. 2021 Jun;21(6):494. doi: 10.3892/ol.2021.12755. Epub 2021 Apr 26.
Numerous studies have reported that abnormal cadherin 3 (CDH3) and microRNA (miRNA/miR)-665 expression can induce the progression of gastric cancer (GC). However, the mechanism of interaction between miR-665 and CDH3 in GC requires further investigation. The present study aimed to investigate the influence of miR-665 and CDH3 in GC development. The effect of miR-665 and CDH3 on GC tissues and cell lines was examined using reverse transcription-quantitative PCR. Subsequently, CDH3 protein expression in GC cell lines was detected using western blotting. To confirm the association between miR-665 and CDH3, a dual-luciferase reporter assay system was employed. Cell proliferation and adhesion were analyzed using BrdU ELISA, MTT and cell adhesion assays. Finally, caspase-3 activity assay kit and FITC apoptosis detection kit were used for the determination of apoptosis of GC cells. The current findings confirmed the upregulation of CDH3 expression in GC cell lines and tissues. Experimental results indicated that CDH3 overexpression increased cell proliferation and adhesion, but decreased the apoptosis level of the cells. Similarly, the miR-665 inhibitor enhanced cell proliferation and adhesion, but inhibited apoptosis of GC cells. Additionally, it was observed that CDH3 was a direct target of miR-665 in GC cells and that miR-665 inhibited CDH3 expression, thereby repressing the progression of GC. In conclusion, the present study suggested that by targeting CDH3, miR-665 suppressed the progression of GC. These findings may provide a significant theoretical basis for future GC clinical therapy.
众多研究报告称，异常的钙黏蛋白3（CDH3）和微小RNA（miRNA/miR）-665表达可诱导胃癌（GC）进展。然而，miR-665与CDH3在胃癌中的相互作用机制仍需进一步研究。本研究旨在探讨miR-665和CDH3在胃癌发生发展中的作用。采用逆转录-定量PCR检测miR-665和CDH3对胃癌组织和细胞系的影响。随后，用蛋白质免疫印迹法检测胃癌细胞系中CDH3蛋白的表达。为证实miR-665与CDH3之间的关联，采用双荧光素酶报告基因检测系统。使用BrdU ELISA、MTT和细胞黏附实验分析细胞增殖和黏附情况。最后，使用caspase-3活性检测试剂盒和FITC凋亡检测试剂盒测定胃癌细胞的凋亡情况。目前的研究结果证实了CDH3在胃癌细胞系和组织中的表达上调。实验结果表明，CDH3过表达增加了细胞增殖和黏附，但降低了细胞的凋亡水平。同样，miR-665抑制剂增强了细胞增殖和黏附，但抑制了胃癌细胞的凋亡。此外，观察到CDH3是胃癌细胞中miR-665的直接靶点，miR-665抑制CDH3表达，从而抑制胃癌进展。总之，本研究表明，miR-665通过靶向CDH3抑制了胃癌进展。这些发现可能为未来胃癌的临床治疗提供重要的理论依据。
