MicroRNA-145 suppresses gastric cancer progression by targeting Hu-antigen R
MicroRNA-145 suppresses gastric cancer progression by targeting Hu-antigen R
复制标题
MicroRNA-145 通过靶向 Hu 抗原 R 抑制胃癌进展
DOI：
10.1152/ajpcell.00118.2019
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发表时间：
2020-03-01
影响因子：
5.5
通讯作者：
Huang, Chen
中科院分区：
文献类型：
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作者：
Li, Qian;Tong, Dongdong;Huang, Chen
Hu抗原R（HuR）参与多种癌症的发生和进展。然而，其在胃癌（GC）中的确切作用和相关分子机制仍不清楚。在本研究中，我们发现HuR在GC组织和细胞系中的表达水平高于邻近正常组织和正常胃上皮细胞系，并且这种升高的表达被发现与淋巴结转移具有显着相关性。此外，通过 RNA 干扰沉默 HuR 可抑制细胞活力，并通过 GC 细胞中的凋亡相关调节因子（Bcl-2 和 Bax）诱导细胞凋亡。此外，生物信息学分析显示，GC组织样本中HuR表达与miR-145表达呈负相关，双荧光素酶报告基因将HuR确定为miR-145的直接靶标。 miR-145 的强制表达在 mRNA 和蛋白质水平上抑制 HuR 表达，并在 GC 细胞中诱导与沉默 HuR 类似的生物学效应。此外，我们还发现恢复HuR可以消除GC细胞中miR-145诱导的影响。总而言之，这些发现证明了 miR-145-HuR 轴在 GC 进展中的确切作用，并表明了 GC 治疗的潜在靶点。
Hu-antigen R (HuR) is involved in the carcinogenesis and progression of multiple types of cancer. However, its precise role in gastric cancer (GC) and the relevant molecular mechanism remain largely unclear. In the present study, we found that HuR expression level was higher in GC tissues and cell lines than in adjacent normal tissues and normal gastric epithelial cell lines, and this elevated expression was found to have a significant association with lymph node metastasis. Moreover, silencing HuR with RNA interference inhibited cell viability and induced cell apoptosis through the apoptosis-related regulators (Bcl-2 and Bax) in GC cells. In addition, bioinformatic analysis revealed that HuR expression was inversely correlated with miR-145 expression in GC tissue samples, and HuR was identified as a direct target of miR-145 with the dual-luciferase reporter. Enforced expression of miR-145 inhibited the HuR expression at both mRNA and protein levels and induced similar biologic effects of silencing HuR in GC cells. Additionally, we also found that restoration of HuR could eliminate the effects induced by miR-145 in GC cells. Taken together, these findings demonstrate the exact role of the miR-145-HuR axis in the progression of GC and indicate a potential target for GC therapy.