A novel nanoplatform-based circCSNK1G3 affects CBX7 protein and promotes glioma cell growth.

Bioenvironmental and biological factors have the potential to contribute to the development of glioma, a type of brain tumor. Recent studies have suggested that a unique circular RNA called circCSNK1G3 could play a role in promoting the growth of glioma cells. It does this by stabilizing a specific microRNA called miR-181 and reducing the expression of a tumor-suppressor gene known as chromobox protein homolog 7 (CBX7). To further investigate circCSNK1G3 and its effects on glioma, we utilized a nanoplatform called adeno-associated virus (AAV)-RNAi.To explore the functional implications of circCSNK1G3, we employed siRNA to silence its expression. Along with these effects, the silencing of circCSNK1G3 led to a depletion of miR-181d and an upregulation of CBX7. When we introduced miR-181d mimics, which artificially increase the levels of miR-181d, the anti-glioma cell activity induced by circCSNK1G3 siRNA was almost completely reversed. Conversely, inhibiting miR-181d mimicked the effects of circCSNK1G3 silencing. Moreover, when we overexpressed circCSNK1G3 in glioma cells, we observed an elevation of miR-181d and a depletion of CBX7. We found that the growth of A172 xenografts (tumors) carrying circCSNK1G3 shRNA was significantly inhibited. In these xenograft tissues, we detected a depletion of circCSNK1G3 and miR-181d, as well as an upregulation of CBX7.

Cyclic nucleotide signaling in sensory neuron hyperexcitability and chronic pain after nerve injury.

The cyclic nucleotide signaling, including cAMP-PKA and cGMP-PKG pathways, has been well known to play critical roles in regulating cellular growth, metabolism and many other intracellular processes. In recent years, more and more studies have uncovered the roles of cAMP and cGMP in the nervous system. The cAMP and cGMP signaling mediates chronic pain induced by different forms of injury and stress. Here we summarize the roles of cAMP-PKA and cGMP-PKG signaling pathways in the pathogenesis of chronic pain after nerve injury. In addition, acute dissociation and chronic compression of the dorsal root ganglion (DRG) neurons, respectively, leads to neural hyperexcitability possibly through PAR2 activation-dependent activation of cAMP-PKA pathway. Clinically, radiotherapy can effectively alleviate bone cancer pain at least partly through inhibiting the cancer cell-induced activation of cAMP-PKA pathway. Roles of cyclic nucleotide signaling in neuropathic and inflammatory pain are also seen in many other animal models and are involved in many pro-nociceptive mechanisms including the activation of hyperpolarization-activated cyclic nucleotide (HCN)-modulated ion channels and the exchange proteins directly activated by cAMP (EPAC). Further understanding the roles of cAMP and cGMP signaling in the pathogenesis of chronic pain is theoretically significant and clinically valuable for treatment of chronic pain.