Department of Internal Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People's Republic of China.
Department of Digestive Disease, The Second Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
J Cell Physiol. 2019 Aug;234(10):18587-18601. doi: 10.1002/jcp.28497. Epub 2019 Apr 5.
Gastric cancer (GC) is a common heterogeneous disease. The critical roles of microRNA-340 (miR-340) in the development and progression of GC were emphasized in accumulating studies. This study aims to examine the regulatory mechanism of miR-340 in GC cellular processes. Initially, microarray technology was used to identify differentially expressed genes and regulatory miRs in GC. After that, the potential role of miR-340 in GC was determined via ectopic expression, depletion, and reporter assay experiments. Expression of secreted phosphoprotein 1 (SPP1), miR-340, phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway, and epithelial-mesenchymal transition (EMT)-related genes was measured. Moreover, to further explore the function of miR-340 in vivo and in vitro, proliferation, apoptosis, migration, invasion, and tumorigenic capacity were evaluated. SPP1 was a target gene of miR-340 which could then mediate the PI3K/AKT signaling pathway by targeting SPP1 in GC. Furthermore, miR-340 levels were reduced and SPP1 was enriched in GC tissues and cells, with the PI3K/AKT signaling pathway being activated. Inhibitory effects of upregulated miR-340 on SPP1 and the PI3K/AKT signaling pathway were confirmed in vivo and in vitro. Overexpression of miR-340 or the silencing of SPP1 inhibited GC cell proliferation, invasion, migration, and EMT process, but promoted apoptosis of GC cells. Typically, targeting of SPP1 by miR-340 may contribute to the inhibition of proliferation, migration, invasion, and EMT of GC cells via suppression of PI3K/AKT signaling pathway.
胃癌（GC）是一种常见的异质性疾病。在积累的研究中强调了 microRNA-340（miR-340）在 GC 发生和发展中的关键作用。本研究旨在研究 miR-340 在 GC 细胞过程中的调控机制。首先，使用微阵列技术鉴定 GC 中差异表达的基因和调节性 miR。之后，通过过表达、耗竭和报告基因检测实验确定 miR-340 在 GC 中的潜在作用。检测分泌磷蛋白 1（SPP1）、miR-340、磷脂酰肌醇 3-激酶/蛋白激酶 B（PI3K/AKT）通路和上皮-间充质转化（EMT）相关基因的表达。此外，为了进一步探索 miR-340 在体内和体外的功能，评估了增殖、凋亡、迁移、侵袭和致瘤能力。SPP1 是 miR-340 的靶基因，可通过靶向 SPP1 介导 GC 中的 PI3K/AKT 信号通路。此外，miR-340 水平降低且 SPP1 在 GC 组织和细胞中丰富，PI3K/AKT 信号通路被激活。体内和体外实验证实，上调 miR-340 对 SPP1 和 PI3K/AKT 信号通路具有抑制作用。过表达 miR-340 或沉默 SPP1 可抑制 GC 细胞增殖、侵袭、迁移和 EMT 过程，但促进 GC 细胞凋亡。通常，miR-340 通过靶向 SPP1 抑制 PI3K/AKT 信号通路可能有助于抑制 GC 细胞的增殖、迁移、侵袭和 EMT。
