Nucleolar protein 7 facilitates melanoma progression and metastasis via HIF-1ɑ/PI3K/AKT/ERK axis

Background: Metastasis is the cause of most fatalities in cancer patients and is poorly understood. Discovery of the underlying determinant and regulatory networks implicated in the cancer cell metastasis is urgently needed. Methods: The expression pattern of nucleolar protein 7 (NOL7) was examined by IHC in clinic melanoma samples. Loss-of-function in melanoma cells was achieved through siRNA and CRISPR/Cas9 system. Assays for proliferation, apoptosis and aggressiveness were performed for functional verification. Immunoblotting and qRT-PCR were used to measure the alterations in proteins and mRNA. Orthotopic xenograft nude mouse model was established to assess the effects of NOL7 on melanoma tumorigenicity and metastatic potential. Results: NOL7 expression was increased with melanoma progression. Abrogation of NOL7 expression led to the dysfunction of malignant behaviors including proliferation, invasion, and anoikis-resistance of melanoma cells in vitro . Depletion of NOL7 expression suppressed melanoma growth and metastasis in vivo . Mechanistically, NOL7 was found to be induced by HIF-1ɑ under hypoxic condition and inhibition of NOL7 reduced the phosphorylation of AKT and ERK protein. Conclusion: This study revealed the cancer-promoting activity of NOL7 in melanoma cells and identified a novel regulatory mechanism of HIF-1ɑ/NOL7/PI3K/AKT/ERK axis in melanoma. NOL7 can function as a novel alert marker and therapeutic target for melanoma treatment.