microRNA-222 Targeting PTEN Promotes Neurite Outgrowth from Adult Dorsal Root Ganglion Neurons following Sciatic Nerve Transection

Abstract

Dorsal root ganglia (DRG) neurons spontaneously undergo neurite growth after nerve injury. MicroRNAs (miRNAs), as small, non-coding RNAs, negatively regulate gene expression in a variety of biological processes. The roles of miRNAs in the regulation of responses of DRG neurons to injury stimuli, however, are not fully understood. Here, microarray analysis was performed to profile the miRNAs in L4-L6 DRGs following rat sciatic nerve transection. The 26 known miRNAs were differentially expressed at 0, 1, 4, 7, 14 d post injury, and the potential targets of the miRNAs were involved in nerve regeneration, as analyzed by bioinformatics. Among the 26 miRNAs, microRNA-222 (miR-222) was our research focus because its increased expression promoted neurite outgrowth while it silencing by miR-222 inhibitor reduced neurite outgrowth. Knockdown experiments confirmed that phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a major inhibitor of nerve regeneration, was a direct target of miR-222 in DRG neurons. In addition, we found that miR-222 might regulate the phosphorylation of cAMP response element binding protein (CREB) through PTEN, and c-Jun activation might enhance the miR-222 expression. Collectively, our data suggest that miR-222 could regulate neurite outgrowth from DRG neurons by targeting PTEN.

MiR-142-3p Enhances Cell Viability and Inhibits Apoptosis by Targeting CDKN1B and TIMP3 Following Sciatic Nerve Injury

“…In total, sixty two adult male Sprague-Dawley (SD) rats (180–220g) were subjected to surgical transection of the sciatic nerve in the thigh as described previously [18]. In brief, the rats were anaesthetized with pentobarbital via intraperitoneal injection, the sciatic nerve was exposed and lifted through an incision on the left lateral thigh.…”

Noncoding RNAs and Their Potential Therapeutic Applications in Tissue Engineering

“…Neural stem/progenitor cells Promote proliferation miR-25 [12]; miR-137 [13]; miR-184 [14]; miR-195 [15] Induce differentiation miR-9, siRNA-TLX [16]; let-7d [17]; miR-137 [13]; miR-184 [14]; miR-195 [15]; miR-34a [18]; lncRNA-BDNF-AS, siRNA-BDNF-AS [19] Mesenchymal stem cells Induce differentiation miR-9 [20]; miR-124 [21] Reduce differentiation miR-128 [22] Neuronal cells Inhibit cell death miR-223 [23]; miR-181c [24]; miR-592 [25]; miR-424 [26]; miR-23a-3p [27]; miR-23a/b, miR-27a/b, siRNA-Apaf-1 [28] Promote cell death miR-134 [29]; miR-200c [30]; miR-30a/b [31][32][33]; miR-124 [34]; miR-711 [35] Regulate degeneration and apoptosis miR-20a [36]; miR-29b [37]; miR-146a, siRNA-miR146a [38] Promote neurite outgrowth miR-7 [39]; miR-21 [40]; miR-222, siRNA-PTEN [41]; miR-8 [42]; miR-431 [43]; miR-145 [44]; lncRNA-uc.217 [45]; miR-138, siRNA-SIRT1 [46] Microglial cells Inhibit inflammation let-7c [47]; miR-124, siRNA-C/EBP-α [48] Promote pro-inflammation miR-155 [49] Inhibit activation let-7c-5p [50] Astrocytes P...…”

“…In spinal cord injury, miR-20a causes motor neuron degeneration by targeting Ngn1 [36], and miR-29b regulates neuronal apoptosis by reducing the expression of Bad, Bim, Puma, and Noxa [37]. Following peripheral nerve injury, overexpression of miR-21 and miR-222 reduces apoptosis and enhances the viability of cultured dorsal root ganglion (DRG) neurons [40,41]. miR-146a mediates apoptosis in DRG neurons under hyperglycemic conditions [38].…”

“…miR-21 and miR-222 promote neurite outgrowth by targeting Sprouty2 and PTEN, respectively [40,41]. miR-8, miR-431, miR-145, and miR-138 have been shown to play regulatory roles in neurite outgrowth [42][43][44]46].…”

The brake within: Mechanisms of intrinsic regulation of axon growth featuring the Cdh1-APC pathway

“…promotes axon growth in adult dorsal root ganglion neurons [63]. Among the microRNAs, that are upregulated in dorsal root ganglia after nerve injury, miR-222 was identified and found to target PTEN [64], suggesting that the injuryresponse disengages inhibitory mechanisms to stimulate regeneration in the PNS, which could be useful in designing therapies for CNS injuries.…”