Journal
BIOLOGY OPEN
Volume 8, Issue 8, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/bio.042937
Keywords
miRNA-138; HIF1 alpha; Melanoma; Proliferation; Invasion; Metastasis
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Funding
- Nansha Science and Technology Project [2016MS001]
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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.
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