MiR-4458/human antigen R (HuR) modulates PBX3 mRNA stability in melanoma tumorigenesis.

Melanoma, a malignancy of the melanocyte, is characterized as the most fatal skin cancer with an increasing incidence. Of note, in spite of great attempts made for better treatment, the therapeutic outcome is barely satisfactory. Abnormal expression of microRNAs (miRNAs) acting as oncogenes or tumor suppressor genes, is frequently implicated in multiple human cancers, including melanoma. Here, we found that miRNA-4458, a reportedly tumor-suppressive miRNA in several cancers, was downregulated in melanoma cells. Besides, our findings indicated that microRNA-4458 (miR-4458) hindered cell proliferation and migration, yet induced apoptosis in melanoma. Mechanical interaction of miR-4458 and PBX3 mRNA, thereby inhibiting PBX3 expression in melanoma cells, was also presented in this work. Human antigen R (HuR) was reported to be greatly upregulated in diverse cancers and HuR-dependent stabilization of target gene contributed a lot to tumor progression. In this study, it revealed the stabilization of PBX3 mRNA by HuR, thereby boosting PBX3 expression. Lastly, we concluded that miR-4458 and HuR modulated the expression of PBX3 in a competitive manner in melanoma tumorigenesis, which might yield a novel insight into the molecular pathogenesis of melanoma.