MicroRNA-144 functions as a tumor suppressor in gastric cancer by targeting cyclooxygenase-2
MicroRNA-144 functions as a tumor suppressor in gastric cancer by targeting cyclooxygenase-2
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DOI：
10.3892/etm.2018.5763
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发表时间：
2018-03-01
影响因子：
2.7
通讯作者：
Xue, Yingwei
中科院分区：
文献类型：
--
作者：
Yao, Qiang;Gu, Anxin;Xue, Yingwei
胃癌是一种严重威胁公共卫生的疾病，其5年生存率低。微小RNA（miRNAs/miRs）在肿瘤发生过程中通过调节细胞增殖、凋亡、迁移和侵袭发挥致癌或抑癌功能，并且已经证明它们在各种类型的癌症中可能失调。目前的研究表明，miR-144和GATA 4在GC组织和细胞系中下调，并表明这可能是由于超甲基化。此外，miR-144和GATA 4通过抑制细胞增殖、诱导细胞周期阻滞和凋亡对GC细胞具有协同作用。生物信息学和荧光素酶报告基因分析结果表明，环氧化酶-2（考克斯-2）是miR-144的直接作用靶点，miR-144可负调控考克斯-2的表达，从而抑制胃癌细胞的生长。GATA 4对考克斯-2也有类似的作用。综上所述，本研究的结果可能会提高对miR-144和GATA 4在GC中的潜在机制的理解。
Gastric cancer (GC) poses a serious public health threat and the 5-year survival rate of patients with GC is low. MicroRNAs (miRNAs/miRs) may serve oncogenic or tumor suppressor functions during tumorigenesis by regulating cell proliferation, apoptosis, migration and invasion and it has been demonstrated that they may be dysregulated in various types of cancer. The present study demonstrated that miR-144 and GATA4 were downregulated in GC tissues and cell lines and suggested that this may be due to hypermethylation. Additionally, miR-144 and GATA4 had synergistic effects on GC cells by repressing cell proliferation and inducing cell cycle arrest and apoptosis. The results of bioinformatics and a luciferase reporter assay indicated that cyclooxygenase-2 (COX-2) is a direct target of miR-144 and that miR-144 negatively regulated the expression of COX-2, which inhibits the viability of GC cells. GATA4 also induced a similar effect on COX-2. Taken together, the results of the present study may improve understanding of the underlying mechanism of miR-144 and GATA4 in GC.