LncRNA HCP5 promotes neuroblastoma proliferation by regulating miR-186-5p/MAP3K2 signal axis

Neuroblastoma (NB) is the most common solid tumor in children. Studies showed that long-chain noncoding RNA (lncRNA) HCP5 played an important role in tumorigenesis, but its role in NB remained unclear. This study aims to determine the role of HCP5 in NB and its possible molecular mechanism.

We analyzed the expression levels of miRNA-186-5p and HCP5 in neuroblastoma and neuroblastoma cell lines SHSY-5Y, Kelly, NBL-S and SK-N-AS, and explored their roles.

We found that the HCP5 expression was up-regulated in NB tissues and cells. The higher the HCP5 expression in NB cells, the stronger the ability of clone formation. Down regulation of the HCP5 expression inhibited the proliferation of NB cells and the growth of subcutaneous transplanted tumor in nude mice. HCP5 could competitively bind miR-186-5p, while miR-186-5p could target the 3'-UTR of MAP3K2. The expression level of miR-186-5p was down regulated while the expression level of MAP3K2 was up-regulated in NB tissues. The expression level of HCP5 and miR-186-5p, the expression level of miR-186-5p and MAP3K2 were negatively correlated. The decreased proliferation of NB cells induced by down-regulation of HCP5 expression can be counteracted by miR-186-5p inhibitor or MAP3K2, and vice versa.

This study showed that lncRNA HCP5, as ceRNA, regulated MAP3K2 to promote NB progression through competitive binding of miR-186-5p. We revealed a new signaling pathway that mediates NB, which provided a new target for the diagnosis and treatment of NB.