Long non-coding RNA Gm4419 promotes trauma-induced astrocyte apoptosis by targeting tumor necrosis factor α

Traumatic brain injury (TBI) remains a life-threatening disease. Accumulating evidences have showed that neuroinflammatory response is a critical biological event in the progression of TBI induced astrocyte damage. However, the exact mechanisms are not well understood. In this study, we demonstrated that long non-coding RNA (lncRNA) Gm4419 promoted trauma-induced astrocyte apoptosis by up-regulating the expression of inflammatory cytokine tumor necrosis factor alpha (TNF-alpha). We observed that Gm4419 was aberrantly induced after injury on astroglial cells in vitro. Overexpression of Gm4419 in injury-treated astrocytes increased protein expressions of TNF-alpha, Bax, cleaved caspase-3 and cleaved caspase-9, decreased levels of Bcl-2 and CyclinD1, and significantly led to cellular apoptosis. Mechanically, Gm4419 transcript could function as a sponge for miR-466l and miR-466l could target TNF-alpha 3' UTR for degradation and translation inhibition. Therefore, Gm4419 could up-regulate TNF-alpha expression by competitively binding miR-466l and then contribute to inflammatory damage as well as astrocyte apoptosis during TBI. Generally speaking, our findings provide better understandings of the mechanism underlying Gm4419 in trauma-induced neuroinflammation and neurological deficits. Thus, the present study would expand the insight into the novel approaches for TBI therapy. (C) 2017 Elsevier Inc. All rights reserved.