MiR-27a-3p and miR-30b-5p inhibited-vitamin D receptor involved in the progression of tuberculosis

Abstract

BackgroundMicroRNAs (miRNAs) play a vital role in tuberculosis (TB). Vitamin D receptor (VDR), an miRNA target gene, and its ligand, vitamin D3 (VitD3), have been reported to exert protective effects against TB. However, whether miRNAs can affect the progression of TB by targeting VDR has not been reported.Materials and methodsResearch subjects were selected according to defined inclusion criteria. A clinical database of 360 samples was established, including the subjects’ demographic information, miRNA expression profiles and cellular experimental results. Two candidate miRNAs, miR-27a-3p, and miR-30b-5p, were identified by a high-throughput sequencing screen and validated by qRT–PCR assays. Univariate and multivariate statistical analyses were performed. VDR and NF-kB p65 protein levels were detected by Western blot assays. Proinflammatory cytokine expression levels were detected by enzyme-linked immunosorbent assay (ELISA). Luciferase assays and fluorescence-activated cell sorting (FACS) were further applied to elucidate the detailed mechanisms.ResultsDifferential miRNA expression profiles were obtained, and miR-27a-3p and miR-30b-5p were highly expressed in patients with TB. These results showed that the two miRNAs were able to induce M1 macrophage differentiation and inhibit M2 macrophage differentiation. Further experiments showed that the two miRNAs decreased the VDR protein level and increased proinflammatory cytokine secretion by macrophages. Mechanistically, the miRNAs targeted the 3′ untranslated region (3′UTR) of the VDR mRNA and thereby downregulated VDR protein levels by post-transcriptional regulation. Then, due to the reduction in VDR protein levels, the NF-kB inflammatory cytokine signaling pathway was activated, thus promoting the progression of TB.ConclusionOur study not only identified differentially expressed miRNAs between the TB and control groups but also revealed that miR-27a-3p and miR-30b-5p regulate proinflammatory cytokine secretion and macrophage differentiation through VDR in macrophages. Thus, these two miRNAs influence the progression of TB.

Inhibition of inflammation and infiltration of M2 macrophages in NSCLC through the ATF3/CSF1 axis: Role of miR‐27a‐3p

“…miR-27a-3p, which is highly expressed in tuberculosis, can induce M1 macrophage differentiation and inhibit M2 macrophage differentiation by targeting vitamin D receptor. 29 We hypothesized that the effect of miR-27a-3p on macrophage polarization may be related to its regulatory mechanism under different pathological conditions. miRNAs act in almost all aspects of cancer biology.…”

“…This was not consistent with our results that miR‐27a‐3p inhibited M2‐type macrophage polarization by targeting the ATF3/CSF‐1 pathway. miR‐27a‐3p, which is highly expressed in tuberculosis, can induce M1 macrophage differentiation and inhibit M2 macrophage differentiation by targeting vitamin D receptor 29 . We hypothesized that the effect of miR‐27a‐3p on macrophage polarization may be related to its regulatory mechanism under different pathological conditions.…”

The new ceRNA crosstalk between mRNAs and miRNAs in intervertebral disc degeneration

“…MicroRNA (miRNA) is a subtype of noncoding, endogenous transcripts with 21-25 nucleotides in length that modulates gene expression in transcription, post-transcription, and epigenetics (Li et al, 2022;Niu et al, 2022;Xiao et al, 2022;Yang et al, 2022). Dysregulated expression of miRNA has been found to participate in many diseases such as neurological diseases, cardiovascular disease, cancer, and other diseases (Lin et al, 2019;Niu et al, 2020;Zhu et al, 2020;Andreucci et al, 2022).…”