Oncogenic role of HMGA2 in fusion-negative rhabdomyosarcoma cells.

BACKGROUND

Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. There are two subtypes, fusion gene-positive RMS (FP-RMS) and fusion gene-negative RMS (FN-RMS), depending on the presence of a fusion gene, either - or -. These fusion genes are thought to be oncogenic drivers of FP-RMS. By contrast, the underlying mechanism of FN-RMS has not been thoroughly investigated. It has recently been shown that HMGA2 is specifically positive in pathological tissue from FN-RMS, but the role of HMGA2 in FN-RMS remains to be clarified.

METHODS

In this study, we used FN-RMS cell lines to investigate the function of HMGA2. Gene expression, cell growth, cell cycle, myogenic differentiation, tumor formation in vivo, and cell viability under drug treatment were assessed.

RESULTS

We found that was highly expressed in FN-RMS cells compared with FP-RMS cells and that knockdown of in FN-RMS cells inhibited cell growth and induced G1 phase accumulation in the cell cycle and myogenic differentiation. Additionally, we showed using both gain-of-function and loss-of-function assays that was required for tumor formation in vivo. Consistent with these findings, the HMGA2 inhibitor netropsin inhibited the cell growth of FN-RMS.

CONCLUSIONS

Our results suggest that HMGA2 has important role in the oncogenicity of FP-RMS and may be a potential therapeutic target in patients with FN-RMS.