Rao Min, Zhu Yonggang, Zhou Yinan, Cong Xiaoxia, Feng Li
Department of Gastroenterology, The People's Hospital of Jilin Province Changchun 130021, China.
Department of Radiotherapy, China-Japan Union Hospital of Jilin University Changchun 130033, China.
Am J Cancer Res. 2017 Feb 1;7(2):323-333. eCollection 2017.
MicroRNA-122 (miR-122) has been implicated in tumor development and progression in various types of cancers. However, the biological function and regulatory mechanisms of miR-122 in gastric cancer (GC) remain largely unknown. We aimed to determine the biological role and underlying mechanism of miR-122 in GC. Real time quantitative RT-PCR (qRT-PCR) was performed to detect the expression of miR-122 in GC tissues and cell lines. CCK8, wound healing, and transwell assays were conducted to determine the effect of miR-122 on cell proliferation, migration, and invasion, respectively. Target molecules were identified by luciferase activity, quantitative RT-PCR, and western blotting. We found that miR-122 expression was significantly decreased in both GC tissues and cell lines and that reduced expression was significantly associated with aggressive clinicopathological features in patients. We also found that overexpression of miR-122 markedly inhibited proliferation, migration, and invasion in GC cell lines. In addition, cAMP responsive element binding protein 1 (CREB1) was identified as a direct target of miR-122, and its expression was negatively correlated with miR-122 expression in GC tissues ( = -0.711, < 0.001). CREB1overexpression rescued the suppressive effect of miR-122 on GC cell proliferation, migration, and invasion. Moreover, we demonstrated that miR-122 inhibited GC tumorigenesis by repressing CREB1 expression. These findings suggest that miR-122 might function as a tumor suppressor in GC and could serve as a promising candidate for therapeutic applications regarding GC treatment.
微小RNA-122（miR-122）与多种癌症的肿瘤发生和进展有关。然而，miR-122在胃癌（GC）中的生物学功能和调控机制仍不清楚。我们旨在确定miR-122在GC中的生物学作用及潜在机制。采用实时定量逆转录PCR（qRT-PCR）检测GC组织和细胞系中miR-122的表达。分别进行CCK8、伤口愈合和Transwell实验，以确定miR-122对细胞增殖、迁移和侵袭的影响。通过荧光素酶活性、定量RT-PCR和蛋白质免疫印迹法鉴定靶分子。我们发现，GC组织和细胞系中miR-122的表达均显著降低，且表达降低与患者侵袭性临床病理特征显著相关。我们还发现，miR-122的过表达显著抑制了GC细胞系的增殖、迁移和侵袭。此外，环磷酸腺苷反应元件结合蛋白1（CREB1）被鉴定为miR-122的直接靶标，其在GC组织中的表达与miR-122表达呈负相关（r = -0.711，P < 0.001）。CREB1的过表达挽救了miR-122对GC细胞增殖、迁移和侵袭的抑制作用。此外，我们证明miR-122通过抑制CREB1的表达来抑制GC的肿瘤发生。这些发现表明，miR-122可能在GC中发挥肿瘤抑制作用，并有望成为GC治疗的有前景的候选治疗靶点。
