miRNA‑155 expression and role in pathogenesis in spinal tuberculosis‑induced intervertebral disc destruction

Abstract

The current study aimed to investigate microRNA-155 (miR-155) expression in spinal tuberculosis-induced intervertebral disc destruction and its regulatory role in disease pathogenesis. A total of 26 patients with intervertebral disc destruction induced by spinal tuberculosis and 31 healthy individuals were included. Reverse transcription-quantitative polymerase chain reactions, western blot analysis and ELISA were performed to detect mRNA and protein expression levels. A bioinformatics analysis was applied to predict the upstream regulator of matrix metalloproteinase (MMP)13, which was confirmed by dual-luciferase reporter assay. Compared with the control group, mRNA and protein expression levels of MMP13 were significantly increased in the intervertebral disc of patients with spinal tuberculosis. However, miR-155 expression in the intervertebral disc of patients with spinal tuberculosis was significantly decreased compared with the control group. Dual-luciferase reporter assays suggested that miR-155 bound to the 3′-untranslated region of MMP13 to regulate gene expression. In primary annulus fibrosus cells, upregulated miR-155 expression significantly decreased MMP13 expression in the cells and culture supernatant, whereas it increased type II collagen expression. Upregulated MMP13 expression in the intervertebral disc in patients with spinal tuberculosis may be correlated with downregulated miR-155 expression. miR-155 may regulate expression levels of associated proteins in the intervertebral disc via modulating MMP13 expression, which contributes to the disease pathogenesis. The results of the current study may provide the theoretical basis for the diagnosis and treatment of disc damages caused by spinal tuberculosis.

Diagnosis and Treatment of Skipped Multifocal Spinal Tuberculosis Lesions

“…One study by Wang et al 136 showed that miR‐133a can down‐regulate the expression of MMP‐9 to restrain collagen degradation, thus alleviating the intervertebral disc damage caused by tuberculosis. Similar results were observed between miR‐155 and MMP‐13 137 …”

“…Similar results were observed between miR-155 and MMP-13. 137 In addition to ncRNA, several tuberculosis susceptibility genes, such as HLA-DQA1, 138 MCP-1-2258, 139 or MC3R, 140 which can provide the preliminary theoretical and experimental basis for the future treatment and drug development of spinal tuberculosis, have been broadly investigated.…”

An Integrative Network Approach to Identify Common Genes for the Therapeutics in Tuberculosis and Its Overlapping Non-Communicable Diseases

“…The inhibition of AKT by shikonin activated the forkhead box (FOX)O3a/early growth response protein (EGR)1 signaling cascade and enhanced the expression of the target gene Bim, leading to apoptosis in lung cancer cells (Jeung et al, 2016). Increased expression of MMP13 has been reported in patients with spinal tuberculosis (Yang et al, 2019).…”

Differential expression analysis of miRNAs in macrophage-derived exosomes in the tuberculosis-infected bone microenvironment

“…However, current research on the role of miRNAs in tuberculosis has predominantly focused on pulmonary tuberculosis infection, with limited studies on extrapulmonary tuberculosis. Yang et al (2019) revealed that miR-155 was downregulated in spinal tuberculosis and could potentially mediate disc destruction by regulating the expression levels of related proteins in * * Indicates a significant difference between the two comparisons (p < 0.01). In this study, we investigated for the first time the miRNA expression levels in macrophage-derived exosomes from the tuberculosis-infected bone microenvironment using highthroughput sequencing.…”