The protective effects of microRNA-26a in steroid-induced osteonecrosis of the femoral head by repressing EZH2

Abstract

Recently, the role of microRNAs (miRs) in human diseases has been verified. This study was determined to explore the protective effects of microRNA-26a (miR-26a) in steroid-induced osteonecrosis of the femoral head (SONFH) with the involvement of enhancer of zeste homologue 2 (EZH2).Femoral head (FH) samples from SONFH patients and patients with femoral neck fracture were collected, and rat SONFH models were established by Escherichia coli endotoxin combining with large dose steroid pulse assay. The hemorheology, blood lipid, inflammatory factors, and pathologic changes were measured by a series of experiments. Moreover, the detection of osteoblasts, osteoclasts, miR-26a expression, EZH2 expression, osteoprotegerin (OPG) and osteoprotegerin ligand (OPGL), and the apoptosis of osteocytes were conducted. The target relation between miR-26a and EZH2 was clarified by bioinformatics and dual-luciferase reporter gene assay.MiR-26a was poorly expressed, while EZH2 was highly expressed in SONFH, and the elevation of miR-26a could repress EZH2 expression. Elevated miR-26a and reduced EZH2 were able to decelerate the apoptosis of osteocytes, increase osteoblasts, and decrease osteoclasts, resulting in a repression of SONFH progression. Additionally, EZH2 was a target gene of miR-26a. Furthermore, the elevation of EZH2 could reverse the repression of SONFH progression that is induced by elevated miR-26a.We found that up-regulation of miR-26a and knockdown of EZH2 could suppress the development of SONFH, which would contribute to the therapy of SONFH.

The role of hypoxia in the tumor microenvironment and development of cancer stem cell: a novel approach to developing treatment

“… Breast cancer [ 145 ] Head and neck cancer [ 100 ] Oral cancer [ 142 ] Prostate cancer [ 143 ] Pancreatic cancer [ 144 ] Down-regulation Regulation of PTEN, CSC marker Lin28b, suppression of EMT and CSC phenotype [ 142 – 144 ] Blockage of Wnt signaling and suppressing self-renewal and stemness of CSCs [ 145 ] Inhibition of EZH2, and suppression of CSC characteristics [ 146 ] miR-26a Tumor suppressive Anti-invasive, stemness inhibitory [ 147 – 149 ] Gastric cancer [ 150 ] Hepatocellular carcinoma [ 149 ] Breast cancer, prostate cancer, pancreatic cancer, nasopharyngeal carcinoma [ 118 ] ? Suppression of HOXC9 and inhibits its metastatic and stemness features of self-renewal [ 150 ] Inhibition of EZH2, and suppression of CSC characteristics [ 147 , 148 ] and EMT [ 149 ] …”

“…Tumor suppressive Anti-invasive, stemness inhibitory [147][148][149] Gastric cancer [150] Hepatocellular carcinoma [149] Breast cancer, prostate cancer, pancreatic cancer, nasopharyngeal carcinoma [118] ? Suppression of HOXC9 and inhibits its metastatic and stemness features of self-renewal [150] Inhibition of EZH2, and suppression of CSC characteristics [147,148] and EMT [149] some evidence from its role in cancer growth. However, HIF-1α may temporally maintain cancer cells in a quiescent state and conserve their survival as long as oxygen supply is available, where they become more invasive.…”

Integrated Analysis of miRNA-mRNA Regulatory Networks Associated with Osteonecrosis of the Femoral Head

“…For example, miR-155-5p was found to be significantly downregulated in ONFH samples [ 16 ]. miR-148a-3p [ 17 ], miR-23b-3p [ 18 ], and miR-26a [ 19 ] were all reported to play a protective role against ONFH. Recent advancement of genome-wide profiling approaches, such as gene microarray and RNA-sequencing technology, enhances the understanding of miRNA and gene expression profiles in the context of ONFH, providing opportunity to identify novel biomarkers and therapeutic targets for ONFH [ 20 , 21 ].…”

Pro-angiognetic and pro-osteogenic effects of human umbilical cord mesenchymal stem cell-derived exosomal miR-21-5p in osteonecrosis of the femoral head

“…SOX5 has been reported to increase the expression of EZH2 at the mRNA and protein levels, while the knock-down of SOX5 reduces the expression of EZH2 [ 15 ]. The downregulated expression of EZH2 induces angiogenesis and osteogenesis [ 17 , 20 ]. To further explore the relationship between SOX5 and EZH2 in ONFH, we initially analyzed the GSE74089 dataset and found that EZH2 was notably upregulated in the ONFH samples (Fig.…”