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

Melanoma with rapid progression towards metastasis has become the deadliest form of skin cancer. However, the mechanism of melanoma growth and metastasis is still unclear. Here, we found that miRNA-138 was lowly expressed and hypoxia-inducible factor 1 alpha (HIF1 alpha) was highly expressed in patients' melanoma tissue compared with the paracancerous tissues, and they had a significant negative correlation (r=-0.877, P< 0.001). Patients withmiRNA-138(low)/HIF1 alpha(high) signatures were predominant in late stage III/IV of melanoma. Further, bioinformatic analysis demonstrated that miRNA-138 directly targeted HIF1 alpha. We found that the introduction of pre-miRNA-138 sequences to A375 cells reduced HIF1 alpha mRNA expression and suppressed cell proliferation, migration and invasion. Overexpression of miRNA-138 or inhibition of HIF1 alpha significantly suppressed the growth and metastasis of melanoma in vivo. Our study demonstrates the role and clinical relevance of miRNA-138 and HIF1 alpha in melanoma cell growth and metastasis, providing a novel therapeutic target for suppression of melanoma growth and metastasis.