miR‐342‐3p promotes osteogenic differentiation via targeting ATF3

Abstract

Through their multiple targets, microRNAs (miRNAs) are involved in numerous physiological and pathological processes. In this study, miR‐342‐3p was found to be deregulated with ossification of ligament or osteoporosis. We demonstrate that silencing miR‐342‐3p impairs osteoblast activity and matrix mineralization, while over expression of miR‐342‐3p promotes osteoblast differentiation significantly. Moreover, miR‐342‐3p directly targets activating transcription factor 3 (ATF3), which inhibits transcription of pro‐osteogenic differentiation‐associated genes. In addition, there exists a higher frequency of methylation at the CpG island of the Enah/Vasp‐Like (EVL) locus in undifferentiated pre‐osteoblasts; however, demethylation of the EVL CpG island induces over expression of miR‐342‐3p during osteogenic differentiation. This study suggests that miR‐342‐3p may serves as a potential marker for diagnosis and treatment of ossification of ligament and osteoporosis.

miR-27a-3p Targets ATF3 to Reduce Calcium Deposition in Vascular Smooth Muscle Cells

“…In the current study, we suggest that a miRNA is an upstream regulator of ATF3. Indeed, an alternate miRNA, miR-342-3p , targets ATF3 to promote osteogenic differentiation of human mesenchymal stem cells, 67 which implicates the existence of a diverse miRNA-ATF3 network. In this study, we did not address which upstream signals affect the decrease in the expression of miR-27a-3p .…”

DNA methylation of noncoding RNAs: new insights into osteogenesis and common bone diseases

“…It was reported that EVL contained a CpG island in the promoter region, and the CpG island aberrant methylation inhibited miR-342 expression in human colorectal cancer, which was a transcription product of EVL intron [42]. Another article confirmed the effect of miR-342-3p in osteogenic differentiation and explored the regulation mechanism between miR-342-3p and DNA methylation of its hosting gene EVL [37]. They found hypomethylation in the promoter of EVL promoted the miR-342-3p expression in osteogenic differentiation, Li et al [35] miRNA miR-29b MiR-29b targeted DNMT1 and led to the methylation modification in the Notch1 promoter, which affected the Notch signaling pathway and regulated the osteogenic differentiation in BMSCs.…”

“…Han et al [37] lncRNA H19 H19 has a strong osteogenic effect via the NOTCH1 pathway, and hypomethylation in the H19 promoter was associated with the high expression of H19.…”

Non‐coding RNAs in bone remodelling and bone metastasis: Mechanisms of action and translational relevance

“…2018), miR-342-3p (Y. Han et al, 2018), miR-451a (Karvande et al, 2018), and miR-874 (Lin et al, 2018). In addition, it has recently been reported that miR-21 and miR-218 play a physiological role in osteocytes, which are differentiated OBs embedded in the bone matrix (Davis et al, 2017).…”