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

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.

circ‑LRP6 contributes to osteosarcoma progression by regulating the miR‑141‑3p/HDAC4/HMGB1 axis

“…In addition, Wen et al (11) reported that circ_HIPK3 promoted OS cell proliferation, migration and invasion by regulating miR-637 and HDAC4 signaling. As a tumor suppressor-related miRNA, miR-141-3p has been reported to serve as a tumor suppressor in several types of cancer, including OS (24)(25)(26)(27). With use of a Circular RNA Interactome database, the present study predicted that circ-LRP6 may have a binding site with miR-141-3p, which was confirmed by dual luciferase assay.…”

“…Previous studies have demonstrated that miRNAs can bind to the 3′-UTRs of target genes to achieve post-transcriptional regulation, thereby modulating the occurrence and progression of related diseases ( 20 - 25 , 45 , 63 ). In the present study, TargetScan bioinformatics analysis and luciferase assays confirmed that miR-141-3p bound to the 3′-UTR of HDAC4 and HMGB1.…”

“…A large number of miRNAs have been reported to participate in OS progression, including miR-873, miR-9, miR-708-5p, miR-183 and miR-17-5p (19)(20)(21)(22)(23). miR-141-3p functions as a tumor suppressor in OS, colorectal cancer and gastric cancer (24)(25)(26)(27). Additionally, in recent years, a number of studies have demonstrated that circRNAs can competitively bind to miRNAs, thereby eliminating the regulatory effect of miRNAs on their target genes and participating in tumor progression (28,29).…”

“…SII). miR-141-3p was selected for further analysis as the matched-degree between miR-141-3p and circ-LRP6 was relatively high compared with other matches, and due to the fact that miR-141-3p has been previously demonstrated to function as a tumor suppressor gene (24)(25)(26)(27). Fig.…”

Long non‑coding RNA CTBP1‑AS2 upregulates USP22 to promote pancreatic carcinoma progression by sponging miR‑141‑3p

“…miR-141-3p expression is reported to be decreased and act as a tumor suppressor in several types of tumors. For example, miR-141-3p expression is downregulated in osteosarcoma; miR-141-3p targets FUS to degrade L-lactate dehydrogenase B chain to reduce the degree of malignancy of osteosarcoma ( 22 ). In addition, miR-141-3p suppresses colorectal cancer cell proliferation, migration and invasion by targeting TNF receptor-associated factor 5 ( 23 ).…”