MicroRNA-181a is elevated by 10-hydroxycamptothecin and represses lung carcinoma progression by downregulating FOXP1

[摘要] Tumor progression is usually characterized by proliferation, migration, and angiogenesis, which is essential forsupplying both nutrients and oxygen to the tumor cells. Therefore, targeting angiogenesis has been considered apromising therapeutic strategy for cancer prevention and treatment. In the present study, we demonstrated that inaddition to suppressing lung cancer cell proliferation and migration in vitro, 10-hydroxycamptothecin (10-HCPT) isalso capable of inhibiting angiogenesis in vivo with a miR-181a-dependent manner. Mechanistically, by upregulatingmiR-181a, which in turn downregulating FOXP1, 10-HCPT can inhibit the PI3K/Akt/ERK signaling pathwaymediated angiogenesis. Furthermore, reduced levels of miR-181a have been found in both lung cancer cell lines andxenograft with concurrently elevated levels of FOXP1, VEGF, bFGF, and HDGF. Consistent with the findings fromthe in vitro experiments, miR-181a impairs neovascularization in our xenograft model. In summary, our findings havenot only established the anti-oncogenic role of miR-181a in lung cancer angiogenesis but also suggest that 10-HCPTcould be a potential therapeutic reagent for lung cancer treatment.

[学科分类] 仪器

[关键词] microRNA-181a;10-hydroxycamptothecin;Angiogenesis;Lung carcinoma