MicroRNA-143-3p, up-regulated in H. pylori-positive gastric cancer, suppresses tumor growth, migration and invasion by directly targeting AKT2.
MicroRNA-143-3p, up-regulated in H. pylori-positive gastric cancer, suppresses tumor growth, migration and invasion by directly targeting AKT2.
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MicroRNA-143-3p 在幽门螺杆菌阳性胃癌中上调，通过直接靶向 AKT2 抑制肿瘤生长、迁移和侵袭
DOI：
10.18632/oncotarget.15646
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发表时间：
2017-04-25
期刊：
影响因子：
--
通讯作者：
Sun G
中科院分区：
文献类型：
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作者：
Wang F;Liu J;Zou Y;Jiao Y;Huang Y;Fan L;Li X;Yu H;He C;Wei W;Wang H;Sun G
我们以前的研究表明，H。pylori感染与胃癌预后的关系基于这些发现，我们假设H。幽门螺杆菌阳性和阴性胃癌可能表现出不同的生长模式和病理生物学行为，表明不同的癌症进展机制。采用基因芯片技术研究了42例胃癌组织中miRNAs的表达谱，并与21例胃癌组织进行了比较。pylori阳性和21例H.幽门阴性组。采用荧光素酶报告基因分析和western blot检测目的miRNA的潜在靶基因。在本研究中，53个miRNAs在H. pylori阳性和阴性胃癌组织。我们研究了一个候选者miR-143- 3 p的表达和功能，这是H.幽门阳性胃癌组织。我们观察到miR-143- 3 p在胃癌组织和细胞中的表达显著降低，且与晚期和淋巴结转移相关。利用体外功能获得和丧失实验，我们证明miR-143- 3 p负调控细胞生长、凋亡、迁移和侵袭。我们进一步将AKT 2表征为miR-143- 3 p的新的直接靶点。AKT 2表达的敲低模拟了miR-143- 3 p恢复的作用。结论：miR-143- 3 p是一种新的肿瘤抑制性miRNA，通过直接靶向AKT 2基因调控肿瘤的生长、迁移和侵袭。进一步的研究是必要的，以表征胃癌进展的机制，并可能最终有助于其治疗。
Our previous studies have suggested a protective role for H. pylori infection in the prognosis of gastric cancer. Based on those findings, we hypothesized that H. pylori-positive and -negative gastric cancers may exhibit different growth patterns and pathobiological behaviors, indicating different mechanisms of cancer progression. By microarray analysis, we studied miRNAs expression profiles in 42 gastric cancer patients, comparing 21 H. pylori-positive and 21 H. pylori-negative groups. Luciferase reporter assay and western blot were used to examine the potential target genes of the interested miRNA. In the present study, 53 miRNAs were significantly differentially expressed in H. pylori-positive and -negative gastric cancer tissues. We investigated the expression and function of one candidate, miR-143-3p, which was the most significantly increased miRNA in H. pylori-positive gastric cancer tissues. We observed that miR-143-3p expression was significantly decreased in gastric cancer tissues and cells, which correlated with late stage and lymph node metastasis. Using gain- and loss-of-function experiments in vitro, we demonstrate that miR-143-3p negatively regulated cell growth, apoptosis, migration and invasion. We further characterized AKT2 as a novel direct target of miR-143-3p. Knockdown of AKT2 expression mimicked the effects of miR-143-3p restoration. In conclusion, our data suggest that miR-143-3p acts as a novel tumor suppressive miRNA by regulating tumor growth, migration and invasion through directly targeting AKT2 gene. Further investigation is warranted to characterize the mechanisms underlying gastric cancer progression and may eventually contribute to its therapy.