lncRNA DLEU1 Modulates Proliferation, Inflammation, and Extracellular Matrix Degradation of Chondrocytes through Regulating miR-671-5p

Abstract

Long noncoding RNAs (lncRNAs) have been shown to be involved in the development of osteoarthritis. However, the expression, function, and mechanism of DLEU1 in OA development remain largely unclear. The present reference demonstrates that DLEU1 is overexpressed in OA specimens compared to control cartilages. Inflammatory cytokines IL-1β, TNF-α, and IL-6 induce DLEU1 expression in chondrocytes. Ectopic expression of DLEU1 induces chondrocyte proliferation, degradation of ECM, and inflammation mediators such as IL-6, IL-8, and TNF-α secretion. Moreover, we demonstrated that DLEU1 targets miR-671-5p expression in chondrocytes. Overexpression of DLEU1 suppresses miR-671-5p expression in chondrocytes. The expression of miR-671-5p is decreased in OA specimens compared to control cartilages. There is a negative correlation between the expression of miR-671-5p and DLEU1 in OA specimens. Inflammatory mediators IL-1β, TNF-α, and IL-6 suppress miR-671-5p expression in OA specimens. Elevated expression of miR-671-5p suppresses chondrocyte proliferation, degradation of ECM, and secretion of inflammation mediators. DLEU1 overexpression promotes chondrocytes proliferation, degradation of ECM, and secretion of inflammation mediators via regulating miR-671-5p. These results suggested that DLEU1 acts as one destructive role in OA development via regulating miR-671-5p.

Integrated Analysis of Non-Coding RNA and mRNA Expression Profiles in Exosomes from Lung Tissue with Sepsis-Induced Acute Lung Injury

“…Overexpression of mmu-miR-671-5p in the ceRNA network has been shown to inhibit the inflammatory mediators IL-1 β, TNFα, and IL-6, 50 , 54 and mmu-miR-122-5p has been demonstrated to originate from the exosomes of lung tissue. 55 Overexpression of mmu-miR-122-5p can induce severe lung injury, inflammation, and oxidative stress. 55 , 56 Jak3 is a member of the JAK family of tyrosine kinases involved in cytokine receptor-mediated intracellular signal transduction.…”

“… 55 Overexpression of mmu-miR-122-5p can induce severe lung injury, inflammation, and oxidative stress. 55 , 56 Jak3 is a member of the JAK family of tyrosine kinases involved in cytokine receptor-mediated intracellular signal transduction. Inhibition of JAK3 leads to NF, and negative regulation of the B-signaling pathway can reduce the overproduction of cytokines/chemokines.…”

Roles of long noncoding RNAs in human inflammatory diseases

“…LncDLEU1, LOXL1-AS1, and LINC00265 were upregulated in OA specimens and OA chondrocytes. DLEU1 could promote the proliferation of chondrocytes and increase the secretion of IL-6, IL-8, and TNF-α by regulating miR-671-5p [ 35 ]. LOXL1-AS1 silencing attenuated proliferation and inflammation via targeting miR-423-5p/KDM5C in chondrocytes [ 36 ].…”

A review on the role of miR-671 in human disorders

“…miR-671-5p has also been shown to facilitate the effect of lncRNA DLEU1 in the regulation of chondrocytes proliferation, inflammatory responses, and degradation of extracellular matrix ( Wu et al, 2022b ). Moreover, the sponging effect of circ_0043947 on miR-671-5p is involved in the pathoetiology of IL1β-induced chondrocyte damage and pathogenesis of osteoarthritis ( He et al, 2022 ).…”