LncRNA HOTAIRM1 promotes osteogenesis by controlling JNK/AP‐1 signalling‐mediated RUNX2 expression

Abstract

Mesenchymal stem cells (MSCs) have potential ability to differentiate into osteocytes in response to in vitro specific induction. However, the molecular basis underlying this biological process remains largely unclear. In this study, we identify lncRNA HOTAIRM1 as a critical regulator to promote osteogenesis of MSCs. Loss of HOTAIRM1 significantly inhibits the calcium deposition and alkaline phosphatase activity of MSCs. Mechanistically, we find that HOTAIRM1 positively modulates the activity of JNK and c‐Jun, both of which are widely accepted as crucial regulators of osteogenic differentiation. More importantly, c‐Jun is found to be functionally involved in the regulation of RUNX2 expression, a master transcription factor of osteogenesis. In detail, c‐Jun can help recruit the acetyltransferase p300 to RUNX2 promoter, facilitating acetylation of histone 3 at K27 site, therefore epigenetically activating RUNX2 gene transcription. In summary, this study highlights the functional importance of HOTAIRM1 in regulation of osteogenesis, and we characterize HOTAIRM1 as a promising molecular target for bone tissue repair and regeneration.

Reduced LINC00551 expression promotes proliferation and invasion of esophageal squamous cancer by increase in HSP27 phosphorylation

“…Long noncoding RNAs (lncRNAs) are a class of non‐or limited protein‐encoding RNA molecules of 200 or more nucleotides in length (Crespi et al, 2017; Plaza, Menschaert, & Payre, 2017; Schmitt & Chang, 2016). Previous transcriptome studies have revealed that over 90% of the mammalian genome is transcribed into noncoding RNAs (Esteller, 2011; Ulitsky & Bartel, 2013) and accumulating evidence showed that lncRNAs play a crucial role in posttranscriptional regulation of gene expression (Fu et al, 2019; Peng, Liu, & Wu, 2018) and participation in many physiological processes (Li et al, 2017; Tang et al, 2017; Yu et al, 2017; Zhou et al, 2019). Dysregulation of lncRNA expression and functions occurred in different human cancers, like cancer initiation, progression, and metastasis (Gupta et al, 2010; Li et al, 2017; Xu et al, 2013), while aberrant expression of lncRNAs, such as HOTAIR, MALAT1, EGFR‐AS, and CCTA1, was associated with ESCC development and progression (Ge et al, 2013; Tan et al, 2017; Wang et al, 2015; Zhang et al, 2017).…”

LINC00899 Promotes Osteogenic Differentiation and Alleviates Osteoporosis via Targeting miR-374a to Regulate RUNX2

“…Therefore, the regulatory mechanism of RUNX2 during osteogenic differentiation has attracted the attention of many researchers. Fu at al indicated that HOTAIRM1 promoted osteogenesis by modulating JNK and c-Jun activity to activate RUNX2 gene transcription [26]. Chen et al reported that lncRNA AWPPH contributed to non-traumatic osteonecrosis through upregulating RUNX2 [27].…”

LINC00899 promotes osteogenic differentiation and alleviates osteoporosis via targeting miR-374a to regulate RUNX2

“…Therefore, the regulatory mechanism of RUNX2 during osteogenic differentiation has attracted the attention of many researchers. Fu at al indicated that HOTAIRM1 promoted osteogenesis by modulating JNK and c-Jun activity to activate RUNX2 gene transcription [31]. Chen et al reported that lncRNA AWPPH contributed to non-traumatic osteonecrosis through upregulating RUNX2 [32].…”