Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Department of Cariovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Curr Med Sci. 2018 Aug;38(4):582-589. doi: 10.1007/s11596-018-1917-y. Epub 2018 Aug 20.
Non-small-cell lung carcinoma (NSCLC) is one of the most frequently diagnosed malignancies worldwide. Previous studies have shown that microRNA-449b (miR-449b) functions as a tumor suppressor in many cancers. However, the role of miR-449b in NSCLC is still unknown. In the present study, miR-449b was significantly downregulated in NSCLC samples and cell lines. Bioinformatics analysis revealed that 3'-UTR region of leucine rich repeat containing G protein-coupled receptor 4 (LGR4) mRNA had putative complementary sequences to miR-449b,which was further confirmed by the luciferase assay. Western blotting showed that restoration of miR-449b in NSCLC cells decreased the expression of LGR4. Interestingly, over-expression of miR-449b inhibited growth and invasion of NSCLC cells in vitro. Furthermore, ectopic expression of LGR4 reversed miR-449b-suppressed proliferation and invasion of NSCLC cells. Therefore, the data of the present study demonstrate that miR-449b inhibits tumor cell growth and invasion by targeting LGR4 in NSCLC.
非小细胞肺癌（NSCLC）是世界上最常见的恶性肿瘤之一。先前的研究表明，微小 RNA-449b（miR-449b）在许多癌症中作为肿瘤抑制因子发挥作用。然而，miR-449b 在 NSCLC 中的作用尚不清楚。在本研究中，miR-449b 在 NSCLC 样本和细胞系中显著下调。生物信息学分析显示，富含亮氨酸重复序列的 G 蛋白偶联受体 4（LGR4）mRNA 的 3'-UTR 区域具有与 miR-449b 互补的潜在序列，这进一步通过荧光素酶测定得到证实。Western blot 显示，NSCLC 细胞中 miR-449b 的恢复降低了 LGR4 的表达。有趣的是，miR-449b 的过表达抑制了 NSCLC 细胞在体外的生长和侵袭。此外，LGR4 的异位表达逆转了 miR-449b 抑制 NSCLC 细胞增殖和侵袭的作用。因此，本研究的数据表明，miR-449b 通过靶向 NSCLC 中的 LGR4 抑制肿瘤细胞的生长和侵袭。
