MicroRNA-92a-3p enhances functional recovery and suppresses apoptosis after spinal cord injury via targeting phosphatase and tensin homolog

Abstract

Spinal cord injury (SCI) is a neurological disease commonly caused by traumatic events on spinal cords. MiRNA-92a-3p is reported to be down-regulated after SCI. Our study investigated the effects of up-regulated miR-92a-3p on SCI and the underlying mechanisms. SCI mice model was established to evaluate the functional recovery of hindlimbs of mice through open-field locomotion and scored by Basso, Beattie, and Bresnahan (BBB) locomotion scale. Apoptosis of spinal cord cells was determined by flow cytometry. The effects of miR-92a-3p on SCI were detected by intrathecally injecting miR-92a-3p agomiR (agomiR-92) into the mice prior to the establishment of SCI. Phosphatase and tensin homolog (PTEN) was predicted as a target of miR-29a-3p by TargetScan. We further assessed the effects of agomiR-92 or/and overexpressed PTEN on apoptosis rates and apoptotic protein expressions in SCI mice. Moreover, the activation of protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling was determined by Western blot. The results showed that compared with the sham-operated mice, SCI mice had much lower BBB scores, and theapoptosis rate of spinal cord cells was significantly increased. After SCI, the expression of miR-92a-3p was down-regulated, and increased expression of miR-92a-3p induced by agomiR-92 further significantly increased the BBB score and decreased apoptosis. PTEN was specifically targeted by miR-92a-3p. In addition, the phosphorylation levels of Akt and mTOR were up-regulated under the treatment of agomiR-92. Our data demonstrated that the neuroprotective effects of miR-92a-3p on spinal cord safter SCI were highly associated with the activation of the PTEN/AKT/mTOR pathway.

miRNA-92a-3p regulates osteoblast differentiation in patients with concomitant limb fractures and TBI via IBSP/PI3K-AKT inhibition

“…Therefore, miRNA-92a-3p appears to be involved in the regulation of cell maturation, differentiation, apoptosis, and immune regulation. 19,20,46,47 Redell et al 17,18 reported that miRNA-92a-3p expression was upregulated 24 h after injury in TBI patients, a conclusion that agrees with both the clinical and animal model results of our current study. We further elucidated the role of miRNA-92a-3p in fracture healing, by suggesting a novel possible mechanism through which miRNA-92a-3p regulates the expression of IBSP in bone tissue and osteogenic precursor cells.…”

“…17,18 miRNA-92a-3p is a single-stranded, non-coding RNA that has been reported to participate in regulating angiogenesis, inhibiting apoptosis, enhancing chondrocyte production, and inhibiting cartilage degradation. 19,20 Redell et al 18 reported that the expression level of miRNA-92a-3p increases significantly in the first 24 h after mild TBI injury but decreases in severe TBI patients. Thus far, little attention has been paid to the role of miRNA-92a-3p on the differentiation of osteogenic precursor cells into osteoblasts, especially in situations of concomitant fracture and traumatic brain trauma.…”

Human umbilical cord mesenchymal stem cells-derived extracellular vesicles facilitate the repair of spinal cord injury via the miR-29b-3p/PTEN/Akt/mTOR axis

“…Previous literature has shown that PTEN inhibits the Akt/mTOR pathway in the functional recovery after SCI [ 29 ]. The levels of pAKT and pmTOR in SCI rats were reduced significantly and promoted after EV treatment.…”

Apelin alleviated neuroinflammation and promoted endogenous neural stem cell proliferation and differentiation after spinal cord injury in rats

“…SCI, a severe CNS injury that can result in motor and sensory disorders [ 33 ], can be divided into primary and secondary injury [ 34 ]. SCI remain a challenging neurological disorder for which there is currently no cure.…”