Cao Guolei, Fan Peiwen, Ma Ronghui, Wang Qinghe, He Lili, Niu Haiwen, Luo Qin
Department of Respiratory and Neurology, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, China.
Cancer Institution, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, China.
Heliyon. 2023 May 6;9(5):e16079. doi: 10.1016/j.heliyon.2023.e16079. eCollection 2023 May.
This study sought to elucidate the role of microRNA-210 (miR-210) in the occurrence and development of lung adenocarcinoma (LUAD).
The levels of lncRNA miR-210HG and miR-210 in LUAD tissues and corresponding normal tissues were analyzed by real-time quantitative PCR. The expression of the anti-hypoxia factor hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were measured by qRT-PCR and Western blot. The target of miR-210 on HIF-1α was confirmed using TCGA, Western blot and luciferase reporter assay. The regulatory role of miR-210 on HIF-1α and VEGF in LUAD was investigated. The correlation of genes with clinical prognosis was analyzed using bioinformatics methods. The effect of miR-210 on LUAD cells was verified through apoptosis assays.
The expression of miR-210 and miR-210HG was significantly higher in LUAD tissues than in normal tissues. The expression of hypoxia-related indicators HIF-1α and VEGF was also significantly higher in LUAD tissues. MiR-210 suppressed HIF-1α expression by targeting site 113 of HIF-1α, thereby affecting VEGF expression. Overexpression of miR-210 inhibited HIF-1 expression by targeting the 113 site of HIF-1, thereby affecting VEGF expression. Conversely, inhibition of miR-210 resulted in a significant increase in HIF-1α and VEGF expression in LUAD cells. In TCGA-LUAD cohorts, the expression of VEGF-c and VEGF-d genes in LUAD tissues was significantly lower than in normal tissues, while overall survival was worse in LUAD patients with high expression of HIF-1α, VEGF-c and VEGF-d. Apoptosis was significantly lower in H1650 cells after miR-210 inhibition.
This study reveals that miR-210 exerts an inhibitory effect on VEGF expression by down-regulating HIF-1α expression in LUAD. Conversely, inhibition of miR-210 significantly reduced H1650 apoptosis and led to worse patient survival by upregulating HIF-1α and VEGF. These results suggest that miR-210 could serve as a potential therapeutic target for the treatment of LUAD.
本研究旨在阐明微小RNA-210（miR-210）在肺腺癌（LUAD）发生发展中的作用。
采用实时定量PCR分析LUAD组织及相应正常组织中lncRNA miR-210HG和miR-210的水平。通过qRT-PCR和蛋白质免疫印迹法检测抗缺氧因子缺氧诱导因子-1α（HIF-1α）和血管内皮生长因子（VEGF）的表达。利用TCGA数据库、蛋白质免疫印迹法和荧光素酶报告基因检测法确定miR-210对HIF-1α的靶向作用。研究miR-210对LUAD中HIF-1α和VEGF的调控作用。采用生物信息学方法分析基因与临床预后的相关性。通过凋亡检测验证miR-210对LUAD细胞的影响。
LUAD组织中miR-210和miR-210HG的表达明显高于正常组织。LUAD组织中缺氧相关指标HIF-1α和VEGF的表达也明显更高。MiR-210通过靶向HIF-1α的113位点抑制HIF-1α表达，从而影响VEGF表达。MiR-210的过表达通过靶向HIF-1的113位点抑制HIF-1表达，从而影响VEGF表达。相反，抑制miR-210导致LUAD细胞中HIF-1α和VEGF表达显著增加。在TCGA-LUAD队列中，LUAD组织中VEGF-c和VEGF-d基因的表达明显低于正常组织，而HIF-1α、VEGF-c和VEGF-d高表达的LUAD患者总生存期较差。miR-210抑制后，H1650细胞凋亡明显降低。
本研究表明，miR-210通过下调LUAD中HIF-1α表达对VEGF表达发挥抑制作用。相反，抑制miR-210可显著降低H1650细胞凋亡，并通过上调HIF-1α和VEGF导致患者生存期变差。这些结果表明，miR-210可能成为治疗LUAD的潜在治疗靶点。
