Liu Li Ying, Wang Wei, Zhao Lin Yu, Guo Bo, Yang Juan, Zhao Xiao Ge, Hou Ni, Ni Lei, Wang Ai Ying, Song Tu Sheng, Huang Chen, Xu Ji Ru
The Center Laboratory for Biomedical Research, Environment and Genes Related to Diseases Key Laboratory of Education Ministry, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710004, P.R. China.
Department of Orthopaedics, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Int J Oncol. 2014 Sep;45(3):1257-65. doi: 10.3892/ijo.2014.2516. Epub 2014 Jun 24.
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.
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表达下调,并发挥肿瘤抑制作用。然而,miR-126在胃癌中的功能似乎多种多样,且在很大程度上尚不清楚。据报道,miR-126在胃癌中通过靶向Crk基因发挥肿瘤抑制作用,或通过靶向SOX2基因发挥致癌基因作用。我们发现miR-126在胃癌细胞系和组织中的表达降低。肿瘤抑制基因PLK2在SGC-7901细胞中受到miR-126的直接调控。miR-126的过表达不仅抑制了SGC-7901细胞的生长和克隆形成,还在体外诱导了细胞凋亡,而抑制miR-126则轻微促进了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了体内肿瘤生长。在SGC-7901细胞中,PLK2、PI3KR2和Crk受miR-126调控。我们推断,miR-126在胃癌中的功能取决于癌基因和抗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,未来可能成为胃癌的治疗靶点。