miR-215 promotes malignant progression of gastric cancer by targeting RUNX1.
miR-215 promotes malignant progression of gastric cancer by targeting RUNX1.
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DOI：
10.18632/oncotarget.6736
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发表时间：
2016-01-26
期刊：
影响因子：
--
通讯作者：
Shen L
中科院分区：
文献类型：
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作者：
Li N;Zhang QY;Zou JL;Li ZW;Tian TT;Dong B;Liu XJ;Ge S;Zhu Y;Gao J;Shen L
据报道，MIR-215在几种癌症中表达下调，并作为肿瘤抑制因子发挥作用。相反，根据我们的数据，miR-215在胃癌(GC)中优先上调。因此，我们对miR-215在GC中的潜在生物学功能进行了研究。检测77例配对胃癌组织和癌旁非肿瘤组织中MIR-215的表达。通过细胞存活率、集落形成、迁移、侵袭、细胞周期、细胞凋亡和荧光素酶检测以及成瘤和转移分析，分析miR-215的生物学功能。MiR-215在7个胃癌细胞系和77例胃癌组织中的表达显著高于癌旁非肿瘤组织(P<；0.05)，且miR-215在晚期胃癌中的表达更高(III/IV期；P<；0.05)。在GES-1和HGC-27细胞中异位表达miR-215(低miR-215表达)促进细胞生长、迁移、侵袭和转移，而在NCI-N87细胞(高miR-215表达)下调miR-215后，这些作用被逆转。根据荧光素酶的研究，预测了miR-215的潜在靶基因，并证实转录因子和肿瘤抑制因子RUNX1是潜在的靶基因。RUNX1在胃癌组织中的表达较癌旁组织下调(P<；0.05)，并在体外逆转了miR-215的部分功能。MIR-215通过靶向RUNX1促进GC的恶性进展，RUNX1可以部分逆转miR-215的作用。
miR-215 was reported to be downregulated and functioned as a tumor suppressor in several cancers. In contrast, miR-215 was preferentially upregulated in gastric cancer (GC) according to our data. Thus, we studied the potential biological function of miR-215 in GC. miR-215 expression was measured in 77 paired GC tissues and adjacent non-tumor tissues. Biological functions of miR-215 were analyzed using cell viability, colony formation, migration, invasion, cell cycle, apoptosis and luciferase assays as well as via tumorigenicity and metastasis analysis. miR-215 was significantly upregulated in 7 GC cell lines and 77 GC tissues compared to adjacent non-tumor tissues (P < 0.05), and miR-215 expression was greater in advanced GC (stage III/IV; P < 0.05). Ectopic expression of miR-215 in GES-1 and HGC-27 cells (low miR-215 expression) promoted cell growth, migration, invasion, and metastasis, and these were reversed in NCI-N87 cells (high miR-215 expression) after miR-215 downregulation. Potential target genes of miR-215 were predicted and RUNX1, a transcription factor and a tumor suppressor, was confirmed to be potential target according to luciferase studies. RUNX1 was downregulated in GC tissues compared to adjacent non-tumor tissues (P < 0.05), and RUNX1 reversed partial function of miR-215 in vitro. miR-215 promotes malignant progression of GC by targeting RUNX1, and RUNX1 can partially reverse miR-215 effects.