Department of Medical Oncology, Jiamusi Tumor Hospital, Jiamusi 154007, China.
Biochem Biophys Res Commun. 2013 Jun 7;435(3):466-71. doi: 10.1016/j.bbrc.2013.05.010. Epub 2013 May 11.
MicroRNAs (miRNAs) play important roles in the development of various cancers. MiRNA-497 functions as a tumor-suppressor that is downregulated in several malignancies; however, its role in non-small cell lung cancer (NSCLC) has not been examined in detail. Here, we showed that miR-497 is downregulated in NSCLC tumors and cell lines and its ectopic expression significantly inhibits cell proliferation and colony formation. Integrated analysis identified HDGF as a downstream target of miR-497, and the downregulation of HDGF by miR-497 overexpression confirmed their association. Rescue experiments showed that the inhibitory effect of miR-497 on cell proliferation and colony formation is predominantly mediated by the modulation of HDGF levels. Furthermore, tumor samples from NSCLC patients showed an inverse relationship between miR-497 and HDGF levels, and ectopic expression of miR-497 significantly inhibited tumor growth and angiogenesis in a SCID mouse xenograft model. Our results suggest that miR-497 may serve as a biomarker in NSCLC, and the modulation of its activity may represent a novel therapeutic strategy for the treatment of NSCLC patients.
微小 RNA（miRNAs）在各种癌症的发展中发挥着重要作用。miRNA-497 作为一种肿瘤抑制因子，在几种恶性肿瘤中下调；然而，其在非小细胞肺癌（NSCLC）中的作用尚未详细研究。在这里，我们表明 miR-497 在 NSCLC 肿瘤和细胞系中下调，其异位表达显著抑制细胞增殖和集落形成。综合分析确定 HDGF 为 miR-497 的下游靶标，miR-497 过表达下调 HDGF 证实了它们的关联。挽救实验表明，miR-497 对细胞增殖和集落形成的抑制作用主要是通过调节 HDGF 水平介导的。此外，NSCLC 患者的肿瘤样本显示 miR-497 和 HDGF 水平呈负相关，miR-497 的异位表达显著抑制了 SCID 小鼠异种移植模型中的肿瘤生长和血管生成。我们的结果表明，miR-497 可能作为 NSCLC 的生物标志物，调节其活性可能代表治疗 NSCLC 患者的一种新的治疗策略。
