MiR-210 regulates lung adenocarcinoma by targeting HIF-1α

Guolei Cao; Peiwen Fan; Ronghui Ma; Qinghe Wang; Lili He; Haiwen Niu; Qin Luo

doi:10.1016/j.heliyon.2023.e16079

MiR-210 regulates lung adenocarcinoma by targeting HIF-1α

Heliyon. 2023 May 6;9(5):e16079. doi: 10.1016/j.heliyon.2023.e16079. eCollection 2023 May.

Authors

Guolei Cao¹, Peiwen Fan², Ronghui Ma¹, Qinghe Wang¹, Lili He¹, Haiwen Niu¹, Qin Luo¹

Affiliations

¹ Department of Respiratory and Neurology, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, China.
² Cancer Institution, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, China.

Abstract

Object: This study sought to elucidate the role of microRNA-210 (miR-210) in the occurrence and development of lung adenocarcinoma (LUAD).

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: HIF-1α; Lung adenocarcinoma; Overall survival; VEGF; miR-210.