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

Lei Wang

doi:10.1042/bsr20193404

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.

Highlights

As a malignant bone cancer, osteosarcoma (OS) accounts for over one tenth of all solid tumors [1,2]
epithelial-to-mesenchymal transition (EMT)-related proteins were detected and we found that the protein levels of N-cadherin and Vimentin were reduced by lactate dehydrogenase B (LDHB) knockdown, while the protein level of E-cadherin was increased (Supplementary Figure S1A), indicating that silencing of LDHB hampered EMT process
LDHB has been confirmed to express at a high level in OS cells [23], the functional role and molecular mechanism of LDHB have not been researched in OS

Summary

Introduction

As a malignant bone cancer, osteosarcoma (OS) accounts for over one tenth of all solid tumors [1,2]. High expression of messenger RNA (mRNA) lactate dehydrogenase B (LDHB) has been confirmed to correlate with unfavorable prognosis of OS [6]; the mechanism of LDHB in OS triggers our interest. MiR-301a-3p interacted with RBP FXR1 to degraded p21 in oral cancer [15]. As a subtype of non-coding RNAs, miRNAs are single-stranded and highly conserved with approximately 22 nucleotides in length [16]. Both RBPs and miRNAs have been elucidated to promote or. All data supported that overexpression of miR-141-3p restrains fused in sarcoma (FUS)-mediated promotion on mRNA stability of LDHB, repressing cell proliferation, migration and invasion in OS

Materials and methods

Results

Discussion