Department of Oncology, Linyi Third People's Hospital, Shandong, P.R. China.
Department of Cardiology, Linyi Third People's Hospital, Shandong, P.R. China.
Oncol Res. 2018 Dec 27;27(1):19-27. doi: 10.3727/096504018X15193469240508. Epub 2018 Mar 1.
The dysregulation of microRNAs (miRNAs) plays an important function in the onset and progression of gastric cancer (GC). In addition, aberrantly expressed miRNAs affect the chemosensitivity of GC cells to chemotherapeutic drugs. Hence, miRNA-based targeted therapy might be applied to treat patients with GC exhibiting chemotherapeutic resistance. In this study, miRNA-623 (miR-623) expression was downregulated in GC tissues and cell lines. Functional analysis showed that the restored miR-623 expression could inhibit the proliferation of GC cells and enhance their chemosensitivity to 5-FU via the cell apoptosis pathway. Cyclin D1 (CCND1) was identified as a direct target gene of miR-623 in GC. The overexpressed CCND1 in GC tissues was negatively correlated with miR-623 level. The recovered CCND1 expression counteracted the effects of miR-623 on GC cell proliferation, chemosensitivity, and 5-FU-induced apoptosis. Thus, our results suggest that miR-623 might function as a tumor suppressor in GC and could be a promising therapeutic target for patients with GC, especially those with chemotherapeutic resistance.
miRNAs（微小 RNA）的失调在胃癌（GC）的发生和发展中起着重要作用。此外，异常表达的 miRNAs 会影响 GC 细胞对化疗药物的敏感性。因此，基于 miRNA 的靶向治疗可能应用于治疗表现出化疗耐药的 GC 患者。在这项研究中，miR-623（miR-623）在 GC 组织和细胞系中表达下调。功能分析表明，恢复的 miR-623 表达可通过细胞凋亡途径抑制 GC 细胞的增殖并增强其对 5-FU 的化疗敏感性。细胞周期蛋白 D1（CCND1）被鉴定为 GC 中 miR-623 的直接靶基因。GC 组织中过表达的 CCND1 与 miR-623 水平呈负相关。恢复的 CCND1 表达抵消了 miR-623 对 GC 细胞增殖、化疗敏感性和 5-FU 诱导的细胞凋亡的影响。因此，我们的研究结果表明，miR-623 可能在 GC 中作为肿瘤抑制因子发挥作用，并且可能是 GC 患者，特别是化疗耐药患者的有前途的治疗靶点。
