Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
Oncol Rep. 2018 Aug;40(2):943-951. doi: 10.3892/or.2018.6487. Epub 2018 Jun 12.
Lung cancer (LC), as the most common cause of cancer‑related mortality worldwide, is characterized by difficulties in early detection, a high degree of malignancy, poor sensitivity to radiotherapy and chemotherapy, and a low 5‑year survival rate. MicroRNA (miRNA) is a class of small, non‑coding, endogenously expressed RNA that serves vital roles in RNA silencing and post‑transcriptional regulation of gene expression. Previous studies have shown that abnormal expression of miRNA is relevant to various malignant tumors, including lung cancer. In the present study, miR‑150 was found to be significantly upregulated in non‑small cell lung cancer (NSCLC) cells, which also exhibited downregulation of SIRT2. Through downregulation of miR‑150 and/or overexpression of SIRT2 in NSCLC cells (A549 and H1299), in vivo assays revealed that the suppression of miR‑150 and re‑expression of SIRT2 could inhibit NSCLC cell growth. Additionally, the present data demonstrated that miR‑150 regulated NSCLC cell viability and mobility through SIRT2/JMJD2A. Finally, it was demonstrated that silencing of miR‑150 led to inactivation of the AKT signaling pathway, which eventually inhibited the viability and mobility of NSCLC cells. This inhibitory effect of miR‑150 could be exacerbated by upregulation of SIRT2. In conclusion, our results demonstrated that miR‑150 plays an important role in the development of lung cancer by serving as an oncogene via the SIRT2/JMJD2A signaling pathway.
肺癌（LC）是全球癌症相关死亡的最常见原因，其特征为早期检测困难、恶性程度高、对放疗和化疗的敏感性差以及 5 年生存率低。微小 RNA（miRNA）是一类小的、非编码的、内源性表达的 RNA，在 RNA 沉默和基因表达的转录后调控中发挥重要作用。先前的研究表明，miRNA 的异常表达与包括肺癌在内的各种恶性肿瘤有关。在本研究中，发现 miR-150 在非小细胞肺癌（NSCLC）细胞中显著上调，同时 SIRT2 下调。通过下调 NSCLC 细胞（A549 和 H1299）中的 miR-150 和/或过表达 SIRT2，体内实验表明抑制 miR-150 和重新表达 SIRT2 可抑制 NSCLC 细胞生长。此外，本数据表明 miR-150 通过 SIRT2/JMJD2A 调节 NSCLC 细胞活力和迁移。最后，证明沉默 miR-150 导致 AKT 信号通路失活，最终抑制 NSCLC 细胞的活力和迁移。miR-150 的这种抑制作用可通过 SIRT2 的上调而加剧。总之，我们的研究结果表明，miR-150 通过 SIRT2/JMJD2A 信号通路作为癌基因在肺癌的发生发展中发挥重要作用。
