miR-126 inhibits growth of SGC-7901 cells by synergistically targeting the oncogenes PI3KR2 and Crk, and the tumor suppressor PLK2
miR-126 inhibits growth of SGC-7901 cells by synergistically targeting the oncogenes PI3KR2 and Crk, and the tumor suppressor PLK2
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DOI：
10.3892/ijo.2014.2516
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发表时间：
2014-09-01
影响因子：
5.2
通讯作者：
Xu, Ji Ru
中科院分区：
文献类型：
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作者：
Liu, Li Ying;Wang, Wei;Xu, Ji Ru
据报道，微小RNA（miRNA）-126（miR-126）在肺癌、宫颈癌、膀胱癌和前列腺癌中下调并充当肿瘤抑制因子。然而，miR-126在胃癌中的功能似乎是多种多样的，并且在很大程度上是未知的。据报道，miR-126通过靶向Crk基因而作为肿瘤抑制因子，或通过靶向胃癌中的SOX 2基因而作为癌基因。我们发现miR-126在胃癌细胞系和组织中的表达降低。胃癌细胞株SGC-7901中miR-126直接调控PLK 2基因表达。过表达miR-126不仅抑制了SGC-7901细胞的生长和克隆形成，而且诱导了细胞凋亡，而抑制miR-126则略微促进了SGC-7901细胞的增殖。细胞周期不受miR-126的影响。此外，miR-126在异种移植模型中抑制体内肿瘤生长。miR-126对SGC-7901细胞中PLK 2、PI 3 KR 2和Crk的表达具有调控作用。我们推测miR-126在胃癌中的作用依赖于癌基因和抑癌基因之间的协同靶向平衡。我们的研究表明miR-126是一种肿瘤抑制因子，有可能成为胃癌治疗的新靶点。
MicroRNA (miRNA)-126 (miR-126) was reported to be downregulated and to act as a tumor suppressor in cancers of the lung, cervix, bladder and prostate. However, the functions of miR-126 in gastric cancer appear to be diverse and are largely unknown. MiR-126 was reported to act as a tumor suppressor by targeting the Crk gene, or as an oncogene by targeting the SOX2 gene in gastric cancer. We identified that the expression of miR-126 was decreased in gastric cancer cell lines and tissues. PLK2, a tumor suppressor gene, was directly regulated by miR-126 in SGC-7901 cells. Overexpression of miR-126 not only suppressed the growth and clone formation of SGC-7901 cells, but also induced apoptosis in vitro, whereas inhibition of miR-126 slightly promoted SGC-7901 cell proliferation. The cell cycle was not affected by miR-126. Moreover, miR-126 suppressed tumor growth in vivo in a xenograft model. PLK2, PI3KR2 and Crk were regulated by miR-126 in SGC-7901 cells. We infer that the functions of miR-126 in gastric cancer depend on synergistic targeting balance between oncogenes and anti-oncogenes. Our study indicates that miR-126 is a tumor suppressor, which in the future may become a therapeutic target for gastric cancer.