Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin, China.
Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Cell Cycle. 2020 Apr;19(7):825-836. doi: 10.1080/15384101.2020.1731946. Epub 2020 Feb 27.
Studies have found that Lnc LINC00461 is an important regulator of cancer. However, the function of Lnc LINC00461 in NSCLC is not known. Therefore, this experimental design was based on Lnc LINC00461 to explore the pathogenesis of Non-small cell lung cancer (NSCLC). RT-qPCR was used to detect the expression of lnc LINC00461 and miR-30a-5p in NSCLC. The CCK-8 method and Transwell assay were used to detect the effects of lnc LINC00461 and miR-30a-5p on proliferation, migration in NSCLC. Target gene prediction and screening, luciferase reporter assays were used to validate downstream target genes of lnc LINC00461 and miR-30a-5p. The protein expression of ZEB2 was detected by Western blot. The tumor changes in mice were detected by in vivo experiments. Lnc LINC00461 was significantly elevated in NSCLC. Lnc LINC00461 knockdown significantly inhibited proliferation and migration in NSCLC. miR-30a-5p was a direct target of lnc LINC00461 and miR-30a-5p was significantly reduced in NSCLC. shLINC00461 and miR-30a-5p inhibitor partially eliminated the effect of shLINC00461 on cell proliferation. And lnc LINC00461 was negatively correlated with miR-30a-5p expression. ZEB2 was a direct target of miR-30a-5p, and miR-30a-5p mimic and sh lnc LINC00461 significantly reduced ZEB2 expression levels. Finally, In vivo, lnc LINC00461 promoted tumor growth by modulating the miR-30a-5p / ZEB2 axis. In conclusion, LncLINC00461 promoted the progression of NSCLC by the miR-30a-5p / ZEB2 axis, and lnc LINC00461 may be a potential therapeutic target for NSCLC.
研究发现 Lnc LINC00461 是癌症的重要调控因子。然而,Lnc LINC00461 在非小细胞肺癌(NSCLC)中的作用尚不清楚。因此,本实验设计基于 Lnc LINC00461 来探讨非小细胞肺癌(NSCLC)的发病机制。采用 RT-qPCR 检测 NSCLC 中 lnc LINC00461 和 miR-30a-5p 的表达。采用 CCK-8 法和 Transwell 实验检测 lnc LINC00461 和 miR-30a-5p 对 NSCLC 增殖、迁移的影响。采用靶基因预测和筛选、荧光素酶报告基因实验验证 lnc LINC00461 和 miR-30a-5p 的下游靶基因。采用 Western blot 检测 ZEB2 蛋白表达。通过体内实验检测小鼠肿瘤变化。Lnc LINC00461 在 NSCLC 中显著升高。Lnc LINC00461 敲低显著抑制 NSCLC 增殖和迁移。miR-30a-5p 是 lnc LINC00461 的直接靶标,miR-30a-5p 在 NSCLC 中显著降低。shLINC00461 和 miR-30a-5p 抑制剂部分消除了 shLINC00461 对细胞增殖的影响。lnc LINC00461 与 miR-30a-5p 表达呈负相关。ZEB2 是 miR-30a-5p 的直接靶标,miR-30a-5p 模拟物和 sh lnc LINC00461 显著降低 ZEB2 表达水平。最后,体内实验结果表明,lnc LINC00461 通过调节 miR-30a-5p/ZEB2 轴促进肿瘤生长。总之,LncLINC00461 通过 miR-30a-5p/ZEB2 轴促进 NSCLC 的进展,lnc LINC00461 可能是 NSCLC 的潜在治疗靶点。