No abstract

LncRNAs have been recognized as significant regulators in various diseases including neuropathic pain. Although the lncRNA NEAT1 has been reported to be involved in multiple cancers, its biological functions in neuropathic pain still remain unknown. In our present study, a chronic constriction injury (CCI) rat model was established and we found that NEAT1 was greatly upregulated in the spinal cord tissues of CCI rats. Knockdown of NEAT1 can repress neuropathic pain behaviors including mechanical and thermal hyperalgesia. In addition, NEAT1 downregulation inhibited neuroinflammation via inhibiting IL-6, IL-1β, and tumor necrosis factor (TNF)-α in CCI rats. We also observed that miR-381 was decreased significantly in CCI rats. By using bioinformatics analysis, miR-381 was predicted to be a microRNA target of NEAT1, which indicated a negative correlation between miR-381 and NEAT1. Inhibition of NEAT1 can induce miR-381 expression in CCI rats, which indicated a negative correlation between NEAT1 and miR-381. HMGB1, as a downstream target gene of miR-381 was observed to be dramatically increased in CCI rats. miR-381 can modulate HMGB1 expression negatively and meanwhile, NEAT1 was able to regulate HMGB1 through sponging miR-381. Downregulation of HMGB1 can inhibit neuropathic pain behaviors which can be reversed by miR-381 inhibitors. Taken these together, it was indicated that NEAT1 can induce neuropathic pain development in CCI rats via regulating miR-381/HMGB1 axis.

In summary, 13 key miRNAs were found to have a vital function in the pathological progress of AD, as well as the target genes and TFs of these miRNAs. The potential functions of these miRNAs as diagnostic and therapeutic targets of the AD are revealed by the present study.

No abstract

MicroRNAs (miRNAs) exhibit various roles in multiple biological processes and abnormal expression of miR-182-5p has been involved in many diseases. However, the role miR-182-5p in Atherosclerosis (AS) remains poorly understood. In our current investigation, an AS model was established by using oxidized low-density lipoprotein (ox-LDL) in RAW264.7 cells. miR-182-5p was markedly decreased in AS model dose-dependently and time-dependently. Additionally, CD36, oil-red staining levels, TC, and TG were inhibited by miR-182-5p mimics, meanwhile ROS levels, MDA, and cell apoptosis were also restrained with an enhancement of SOD activity. Consistently, opposite results were exhibited when miR-182-5p inhibitors were transfected into RAW264.7 cells. It is well known that toll-like receptor 4 (TLR4) is responsible for many inflammation diseases. By using bioinformatics analysis, TLR4 was indicated as a potential target of miR-182-5p. We observed TLR4 was activated in AS models and miR-182-5p could repress AS progression by targeting TLR4 in vitro. In conclusion, we uncovered that miR-182-5p played significant roles in AS through inhibiting oxidative stress and apoptosis via inactivating TLR4 expression.