MicroRNA-138 negatively regulates the hypoxia-inducible factor 1α to suppress melanoma growth and metastasis

Abstract

ABSTRACTMelanoma with rapid progression towards metastasis becomes the deadliest form of skin cancer. However, the mechanism of melanoma growth and metastasis is still unclear. Here, we found that miRNA-138 was low expression and hypoxia-inducible factor 1α (HIF1α) was high expression in the patient’s melanoma tissue, and they had a significant negative correlation (r = -0.937, P < 0.001). Patients with miRNA-138low/HIF1αhigh signature were predominant in late stage. Further, bioinformatic analysis demonstrated that miRNA-138 directly targeted HIF1α. We found that the introduction of miRNA-138 mimics to A375 cells could reduced HIF1α mRNA expression, and suppressed the cell proliferation, migration and invasion. Overexpression of miRNA-138 or inhibition of HIF1α significantly suppressed the growth and metastasis of melanoma in vivo. Our study demonstrates the role and clinical relevance of miRNA-138 and HIF1α in melanoma cell growth and metastasis, providing a novel therapeutic target for suppression of melanoma growth and metastasis.