MiR-141-3p overexpression suppresses the malignancy of osteosarcoma by targeting FUS to degrade LDHB

MiR-141-3p 过表达通过靶向 FUS 降解 LDHB 抑制骨肉瘤恶性程度

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作者:Lei Wang

Abstract

Osteosarcoma (OS) is a common malignant bone cancer. Lactate dehydrogenase B (LDHB) has been revealed to act as a tumor promoter in several cancers. It is also revealed to be correlated with poor prognosis in OS, but its molecular mechanism in OS remains veiled. Our work illustrated that LDHB was overexpressed in OS tissues and cells, and it could enhance cell proliferation, migration, and invasion in OS. Subsequently, it was confirmed that fused in sarcoma (FUS) could bind with LDHB to positively regulate the stability of LDHB messenger RNA (mRNA). Besides, FUS expression was revealed to be elevated in OS tissues and positively correlate with LDHB expression. Furthermore, miR-141-3p, down-regulated in OS cells, was identified as the upstream regulator of FUS in OS cells. Besides, miR-141-3p overexpression decreased mRNA and protein levels of FUS and LDHB. More importantly, overexpression of miR-141-3p could impair FUS overexpression-mediated promotion on LDHB mRNA stability and expression. Finally, rescue assays indicated that miR-141-3p regulated OS cells cellular process via regulating LDHB. In sum, miR-141-3p targets FUS to degrade LDHB, thereby attenuating the malignancy of OS cells.

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