Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, PR China.
Int J Oncol. 2012 May;40(5):1553-60. doi: 10.3892/ijo.2012.1342. Epub 2012 Jan 24.
MicroRNAs play critical roles in tumorigenesis as either oncogenes or tumor suppressors. As a microRNA induced by Twist, miR-10b function as a metastasis driver in different types of cancer, in which the downstream target gene HOXD10 is the main mediator. In gastric tumor species, miR-10b levels were dramatically elevated in lymphoma node metastasis-positive tumor tissues compared with lymphoma node metastasis-free tumor tissues, and were correlated to dowregulation of HOXD10 expression. In gastric cell lines with distinct degrees of differentiation, miR-10b was highly expressed in the cell line with strong metastatic ability. In MNK45 cells, inhibition of miR-10b led to abrogation of cell invasion. While in GES-1 cells, miR-10 overexpression resulted in enhancement of invasiveness through translational inhibition of HOXD10, and constitutive expression of HOXD10 reversed the effects of miR-10b on cell invasion. Furthermore, either knockdown of RhoC or inhibition of AKT activation interfered miR-10-induced invasiveness in GES-1 cells. In summary, these observations suggest that miR-10b can stimulate the upregulation of RhoC and AKT phosphorylation through targeting HOXD10, thus promoting cell invasion in gastric tumors.
MicroRNAs 在肿瘤发生中发挥关键作用，它们可以作为癌基因或肿瘤抑制因子。作为一种由 Twist 诱导的 microRNA，miR-10b 在不同类型的癌症中作为转移驱动因子发挥作用，其下游靶基因 HOXD10 是主要的介导因子。在胃肿瘤中，miR-10b 在淋巴结转移阳性的肿瘤组织中的水平明显高于淋巴结转移阴性的肿瘤组织，并且与 HOXD10 表达的下调相关。在具有不同分化程度的胃细胞系中，miR-10b 在具有强转移能力的细胞系中高表达。在 MNK45 细胞中，抑制 miR-10b 导致细胞侵袭能力丧失。而在 GES-1 细胞中，miR-10b 通过抑制 HOXD10 的翻译导致侵袭性增强，HOXD10 的组成性表达逆转了 miR-10b 对细胞侵袭的影响。此外，敲低 RhoC 或抑制 AKT 激活会干扰 GES-1 细胞中 miR-10 诱导的侵袭性。总之，这些观察结果表明，miR-10b 可以通过靶向 HOXD10 刺激 RhoC 和 AKT 磷酸化的上调，从而促进胃肿瘤中的细胞侵袭。
