MicroRNA-874 functions as a tumor suppressor in rhabdomyosarcoma by directly targeting GEFT

[摘要] MicroRNA-874 (miR-874) is downregulated and acts as a tumor suppressor gene in several human cancers. Its biological function and underlying molecular mechanism in rhabdomyosarcoma (RMS), however, remain unclear. In this study, we found that miR-874 expression was downregulated in human RMS tissue samples and cell lines through quantitative real-time polymerase chain reaction (qRT-PCR). Functional studies revealed that miR-874 overexpression in RMS cells remarkably inhibited proliferation, invasion, migration, and induced apoptosis. The results of luciferase activity assay, qRT-PCR and western blot analyses showed that miR-874 inhibited GEFT translation and suppressed GEFT expression by directly targeting the 3’-untranslated region (3’-UTR) of GEFT mRNA. GEFT expression was upregulated in RMS tissue samples and cell lines and was inversely correlated with miR-874 expression. Downregulation of GEFT has similar effects to miR-874 overexpression in RMS cells. Notably, GEFT restoration partially reversed the tumor-suppressive effects of miR-874. Our results indicated that miR-874 functions as a tumor suppressor in RMS and may suppress the growth and metastasis of RMS cells partially by targeting GEFT.

[学科分类] 肿瘤学

[关键词] Rhabdomyosarcoma;miR-874;GEFT