State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, China.
Cell Cycle. 2012 Jul 1;11(13):2495-506. doi: 10.4161/cc.20898.
The microRNA miR-138 is dysregulated in several human cancers, but the underlying mechanism remains largely unknown. Here, we report that miR-138 is commonly underexpressed in nasopharyngeal carcinoma (NPC) specimens and NPC cell lines. The ectopic expression of miR-138 dramatically suppressed cell proliferation and colony formation in vitro and inhibited tumorigenesis in vivo. Moreover, we identified the cyclin D1 (CCND1) gene as a novel direct target of miR-138. In consistent with the knocked-down expression of CCND1, overexpression of miR-138 inhibited cell growth and cell cycle progression in NPC cells. Furthermore, CCND1 was widely upregulated in NPC tumors, and its mRNA levels were inversely correlated with miR-138 expression. Taken together, our findings suggest that miR-138 might be a tumor suppressor in NPC, which is exerted partially by inhibiting CCND1 expression. The identification of functional miR-138 in NPC and its direct link to CCND1 might provide good candidates for developing diagnostic markers and therapeutic applications for NPC.
miR-138 在多种人类癌症中失调，但潜在机制在很大程度上仍不清楚。在这里，我们报告 miR-138 在鼻咽癌（NPC）标本和 NPC 细胞系中普遍低表达。miR-138 的异位表达在体外显著抑制细胞增殖和集落形成，并抑制体内肿瘤发生。此外，我们鉴定出细胞周期蛋白 D1（CCND1）基因为 miR-138 的一个新的直接靶标。与 CCND1 的敲低表达一致，miR-138 的过表达抑制 NPC 细胞的生长和细胞周期进程。此外，CCND1 在 NPC 肿瘤中广泛上调，其 mRNA 水平与 miR-138 的表达呈负相关。总之，我们的研究结果表明 miR-138 可能是 NPC 的一种肿瘤抑制因子，部分通过抑制 CCND1 的表达来发挥作用。功能性 miR-138 在 NPC 中的鉴定及其与 CCND1 的直接联系可能为开发 NPC 的诊断标志物和治疗应用提供良好的候选物。
