Long Noncoding RNA Nuclear Enriched Abundant Transcript 1 (NEAT1) Regulates Proliferation, Apoptosis, and Inflammation of Chondrocytes via the miR-181a/Glycerol-3-Phosphate Dehydrogenase 1-Like (GPD1L) Axis

Abstract

Departmental sources Background: Osteoarthritis (OA) is one of the most common chronic musculoskeletal diseases, yet to date it lacks effective therapeutic strategies. Increasing evidence suggests that long noncoding RNAs (lncRNAs) serve pivotal roles in the occurrence and development of OA. However, the possible molecular mechanism involving lncRNAs, such as nuclear enriched abundant transcript 1 (NEAT1), in OA progression is still unclear. Material/Methods: First, NEAT1 and miR-181a expression in OA synovium tissues and normal synovium tissues were detected. Then, the effect of NEAT1 on modulating growth ability, apoptosis, and inflammation in OA chondrocytes was investigated by a series of loss-function experiments. Next, the correlation between NEAT1, miR-181a, and glycerol-3-phosphate dehydrogenase 1-like (GPD1L) was fully investigated. Finally, the downregulation of miR-181a was employed as a recovery experiment to explore the functional mechanism of NEAT1 in OA. Results: In the present study, we found that NEAT1 expression was downregulated in OA tissues, while miR-181a expression was prominently upregulated. Moreover, reduced expression of NEAT1 suppressed cell growth while elevating the apoptotic rate and increasing the abundance of inflammatory cytokines released in OA chondrocytes. Furthermore, we clarified that miR-181a was a direct sponge of NEAT1, and GPD1L was able to bind to miR-181a. Additionally, we found that downregulation of miR-181a was able to attenuate the effect of NEAT1 on apoptosis, inflammatory response, and proliferation in OA chondrocytes. Conclusions: Our findings indicate that downregulation of NEAT1 aggravated progression of OA via modulating the miR-181a/GPD1L axis, providing a novel insight into the mechanism of OA pathogenesis.

Delivery of Long Non-coding RNA NEAT1 by Peripheral Blood Monouclear Cells-Derived Exosomes Promotes the Occurrence of Rheumatoid Arthritis via the MicroRNA-23a/MDM2/SIRT6 Axis

“…Additionally, the in vivo experiments suggested that downregulation of lncRNA NEAT1 shuttled by PBMC-derived exos impeded RA deterioration of mice. It has been demonstrated that lncRNA NEAT1 restricted cell growth, enhanced the apoptotic rate and the in?ammatory cytokines released in OA chondrocytes (Wang et al, 2019). Similar to our results, lncRNA NEAT1 expression was found to be upregulated in OA tissues, and the concentrations of inflammatory factors were declined, cell viability of synoviocyte was inhibited by lncRNA NEAT1 knockdown (Wang et al, 2017).…”

NEAT1 Negatively Regulates Cell Proliferation and Migration of Neuroblastoma Cells by miR-183-5p/FOXP1 Via the ERK/AKT Pathway

“…But overexpression of NEAT1 promoted cell proliferation and suppressed apoptosis in ovarian cancer cells 13 . Researchers also found that downregulation of NEAT1 aggravated progression of osteoarthritis via modulating the miR-181a/GPD1 L axis 14 . As our results showed, NEAT1 was downregulated in NB tissues and cell lines, while upregulation of NEAT1 inhibited the cell proliferation, migration, and invasion in NB cells.…”

Long non-coding RNA NEAT1/miR-338-3p axis impedes the progression of acute myeloid leukemia via regulating CREBRF

“…Xu et al proposed that NEAT1 could mitigate the acuteon-chronic liver failure by blocking the TRAF6-meidated inflammatory response [31], and Zhang et al claimed that the oxidative stress-induced vascular endothelial cell injury was suppressed by NEAT1 through the activation of the miR-181d-5p/CDKN3 axis [32]. And NEAT1 impeded the progression of osteoarthritis via the regulation of miR-181a-GPD1L axis [33]. Additionally, Zeng et al attested that NEAT1 exacerbated cell apoptosis in chronic myeloid leukemia (CML) [34].…”