Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
Department of Pediatrics, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
Biomed Res Int. 2018 Apr 12;2018:5109497. doi: 10.1155/2018/5109497. eCollection 2018.
MicroRNAs (miRNAs or miRs) regulate gene expression at the posttranscriptional level and are involved in many biological processes such as cell proliferation and migration, stem cell differentiation, inflammation, and apoptosis. In particular, miR-144-3p is downregulated in various cancers, and its overexpression inhibits the proliferation and metastasis of cancer cells. However, the role of miR-144-5p in non-small-cell lung cancer (NSCLC), especially radiosensitivity, is unknown. In this study, we found that miR-144-5p was downregulated in NSCLC clinical specimens as well as NSCLC cell lines exposed to radiation. Enhanced expression of miR-144-5p promoted the radiosensitivity of NSCLC cells and A549 cell mouse xenografts . Furthermore, we identified activating transcription factor 2 (ATF2) as the direct and functional target of miR-144-5p using integrated bioinformatics analysis and a luciferase reporter assay. In addition, restoration of ATF2 expression inhibited miR-144-5p-induced NSCLC cell sensitivity to radiation and . Our findings suggest that deregulation of the miR-144-5p/ATF2 axis plays an important role in NSCLC cell radiosensitivity, thus representing a new potential therapeutic target for NSCLC.
微小 RNA（miRNA 或 miR）在后转录水平上调节基因表达，参与许多生物学过程，如细胞增殖和迁移、干细胞分化、炎症和细胞凋亡。特别是，miR-144-3p 在各种癌症中下调，其过表达抑制癌细胞的增殖和转移。然而，miR-144-5p 在非小细胞肺癌（NSCLC）中的作用，特别是放射敏感性，尚不清楚。在本研究中，我们发现 miR-144-5p 在 NSCLC 临床标本和暴露于辐射的 NSCLC 细胞系中下调。miR-144-5p 的增强表达促进了 NSCLC 细胞和 A549 细胞小鼠异种移植物的放射敏感性。此外，我们通过整合生物信息学分析和荧光素酶报告基因测定鉴定激活转录因子 2（ATF2）为 miR-144-5p 的直接和功能靶标。此外，恢复 ATF2 表达抑制了 miR-144-5p 诱导的 NSCLC 细胞对辐射的敏感性。我们的研究结果表明，miR-144-5p/ATF2 轴的失调在 NSCLC 细胞放射敏感性中起重要作用，因此代表 NSCLC 的一个新的潜在治疗靶点。
