MiR‐28‐5p relieves neuropathic pain by targeting Zeb1 in CCI rat models

Abstract

MicroRNAs (miRNAs) are recognized as significant regulators of neuropathic pain. Moreover, neuroinflammation can contribute a lot to the progression of neuropathic pain. MiR-28-5p has been reported to be involved in many pathological diseases. However, little is known about the function of miR-28-5p in neuropathic pain development. Our current study was designed to investigate the biological roles of miR-28-5p in neuropathic pain in a rat model established by chronic sciatic nerve injury (CCI). Here, we observed that miR-28-5p was decreased in CCI rats. MiR-28-5p overexpression was able to alleviate neuropathic pain behaviors including mechanical and thermal hyperalgesia. Meanwhile, inflammation-correlated biomarkers such as Cyclooxygenase 2 (Cox-2), interleukin-6 (IL-6), and IL-1β were greatly promoted in CCI rats and they were inhibited by miR-28-5p upregulation. In addition, zinc finger E-box-binding homeobox 1 (Zeb1) is a kind of transcription factor that is involved in various diseases. Here, in our study, Zeb1 was predicted as a downstream target of miR-28-5p. miR-28-5p can bind with the 3'-untranslated region of Zeb1, which was validated by carrying out dual-luciferase reporter assay. Moreover, we found that Zeb1 was significantly increased in CCI rats and miR-28-5p can modulate Zeb1 expression negatively. Theoverexpression of Zeb1 can disturb neuropathic pain development, which was repressed by the increase of miR-28-5p by upregulating Cox-2, IL-6, and IL-1β levels. By taking all of these together, it was indicated in our study that miR-28-5p can reduce neuropathic pain progression by targeting Zeb1 in vivo. Our data implied that miR-28-5p/Zeb1 axis can be a novel therapeutic target for neuropathic pain treatment.

miR‐194 relieve neuropathic pain and prevent neuroinflammation via targeting FOXA1

“…The secretion of numerous inflammatory cytokines including COX-2, IL-6, and IL-1β promote the neuropathic pain process. 27 Since the role of miR-194 on neuroinflammation in the neuropathic pain process is unknown, we here designed to explore the potential function of miR-194 in neuropathic pain. We first discovered miR-194 was remarkably downregulated in CCI rat abnormally.…”

MicroRNA-28-5p as a potential diagnostic biomarker for chronic periodontitis and its role in cell proliferation and inflammatory response

“…miR-28-5p, as one of the numerous miRNAs, has been reported to be involved in inflammatory responses in a variety of diseases. miR-28-5p upregulation inhibits inflammatory factor expression in rats with chronic sciatic nerve injury 8 and is associated with axial spondylolisthesis. 9 Additionally, miR-28-5p was significantly downregulated in lipopolysaccharide (LPS)-induced myocardial inflammation in rats.…”

miR‑28‑5p inhibits the migration of breast�cancer by regulating WSB2

“…miRNAs regulate gene expression by binding to the 3′UTRs of their target mRNAs, and a single miRNA can regulate the expression of multiple genes. Studies have demonstrated that LPP ( 7 ), RAP1B ( 9 ), NRF2 ( 22 ) and ZEB1 ( 23 ) are direct target genes of miR-28-5p. The present study revealed that RAP1B was downregulated by miR-28-5p, which was consistent with the findings of a previous study ( 9 ).…”