Department of Cardiology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.
Department of Respiratory Medicine, the Second Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.
Oncol Res. 2019 Feb 5;27(2):261-268. doi: 10.3727/096504018X15219188894056. Epub 2018 Apr 3.
miR-223-5p has been demonstrated to regulate the development and progression of various cancers, such as hepatocellular carcinoma, breast cancer, and gastric carcinoma. However, the role of miR-223-5p in non-small cell lung cancer (NSCLC) requires further investigation. In this study, we found that the expression of miR-223-5p was significantly downregulated in NSCLC tissues and cell lines. Moreover, the expression level of miR-223-5p is negatively correlated with the malignance of NSCLC. We found that overexpression of miR-223-5p remarkably suppressed the proliferation of NSCLC cells in vitro and in vivo. miR-223-5p overexpression also led to reduced migration and invasion in NSCLC cells. Mechanistically, we found that E2F8, a key transcription factor involved in many kinds of biological processes, was a direct target gene of miR-223-5p. Overexpression of miR-223-5p significantly decreased the mRNA and protein levels of E2F8 in NSCLC cells. We also showed that restoration of E2F8 rescued the proliferation, migration, and invasion of miR-223-5p-overexpressing NSCLC cells. Taken together, our findings demonstrated that miR-223-5p suppressed NSCLC progression through targeting E2F8.
miR-223-5p 已被证明可调节多种癌症的发展和进展，如肝癌、乳腺癌和胃癌。然而，miR-223-5p 在非小细胞肺癌（NSCLC）中的作用需要进一步研究。在本研究中，我们发现 miR-223-5p 在 NSCLC 组织和细胞系中的表达明显下调。此外，miR-223-5p 的表达水平与 NSCLC 的恶性程度呈负相关。我们发现过表达 miR-223-5p 可显著抑制 NSCLC 细胞在体外和体内的增殖。miR-223-5p 的过表达也导致 NSCLC 细胞迁移和侵袭减少。机制上，我们发现 E2F8，一种参与多种生物过程的关键转录因子，是 miR-223-5p 的直接靶基因。miR-223-5p 的过表达显著降低了 NSCLC 细胞中 E2F8 的 mRNA 和蛋白水平。我们还表明，E2F8 的恢复挽救了 miR-223-5p 过表达 NSCLC 细胞的增殖、迁移和侵袭。总之，我们的研究结果表明，miR-223-5p 通过靶向 E2F8 抑制 NSCLC 进展。
