LncRNA NKILA integrates RXFP1/AKT and NF‐κB signalling to regulate osteogenesis of mesenchymal stem cells

Abstract

Mesenchymal stem cells (MSCs) are previously found to have potential capacity to differentiate into osteocytes when exposed to specific stimuli. However, the detailed molecular mechanism during this progress remains largely unknown. In the current study, we characterized the lncRNA NKILA as a crucial positive regulator for osteogenesis of MSCs. NKILA attenuation significantly inhibits the calcium deposition and alkaline phosphatase activity of MSCs. More interestingly, we defined that NKILA is functionally involved in the regulation of RXFP1/PI3K‐AKT and NF‐κB signalling. Knockdown of NKILA dramatically down‐regulates the expression of RXFP1 and then reduces the activity of AKT, a downstream regulator of RXFP1 signalling which is widely accepted as an activator of osteogenesis. Moreover, we identify NF‐κB as another critical regulator implicated in NKILA‐mediated osteogenic differentiation. Inhibition of NF‐κB can induce the expression of RUNX2, a master transcription factor of osteogenesis, in a HDAC2‐mediated deacetylation manner. Thus, this study illustrates the regulatory function of NKILA in osteogenesis through distinct signalling pathways, therefore providing a new insight into searching for new molecular targets for bone tissue repair and regeneration.

Long noncoding RNA MAPKAPK5-AS1 promotes colorectal cancer progression by cis-regulating the nearby gene MK5 and acting as a let-7f-1-3p sponge

“…Long noncoding RNAs (lncRNAs) are a class of noncoding RNAs with a length greater than 200 nucleotides [6] and are categorized based on regulating gene expression in cis versus performing functions in trans [7]. In recent years, emerging evidence has shown that lncRNAs play major roles in the occurrence and development of cardiovascular disease [8], cardiomyopathy [9] and mesenchymal stem cells [10,11], in particular, dysregulation of lncRNAs has been discovered in many human cancers [12][13][14]. For example, HOX transcript antisense RNA (HOTAIR) is the first lncRNA [15] demonstrated to have a trans-transcriptional regulatory function, and it has been shown to have carcinogenic function in prostate cancer [16] and breast cancer [17,18].…”

Long non-coding RNA MIR22HG promotes osteogenic differentiation of bone marrow mesenchymal stem cells via PTEN/ AKT pathway

“…For example, Wu et al showed that lncRNA HIF1A-AS2 promoted osteogenic differentiation of adipose-derived stem cells through activating the PI3K/AKT signaling pathway 34 . Zhang et al reported that AKT signaling was involved in lncRNA NKILA-mediated osteogenic differentiation in mesenchymal stem cells 35 .…”

Macrophage Long Non-Coding RNAs in Pathogenesis of Cardiovascular Disease

“…LncRNAs have been found to both upregulate and suppress immune-responsive genes. Several of these lncRNAs have now substantiated roles in the regulation of NF-κB signaling in many human disease models in mice, including CVD [111,[114][115][116][117][118][119][120][121][122][123][124]. The crosstalk between lncRNAs and NF-κB signaling is complex, involving both direct and indirect mechanisms and spanning from epigenetic control and even to post-translational modifications.…”