Biochemical and biophysical research communications, 2017-09, Vol.491 (2), p.478-485
2017
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- Autor(en) / Beteiligte
- Titel
- Long non-coding RNA Gm4419 promotes trauma-induced astrocyte apoptosis by targeting tumor necrosis factor α
- Ist Teil von
- Biochemical and biophysical research communications, 2017-09, Vol.491 (2), p.478-485
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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 α (TNF-α). 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-α, 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-α 3′ UTR for degradation and translation inhibition. Therefore, Gm4419 could up-regulate TNF-α 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. [Display omitted] •Gm4419 is induced in astrocytes after trauma injury.•Gm4419 promotes trauma-induced astrocyte apoptosis.•Gm4419 functions as a sponge for miR-466l.•miR-466l targets TNF-α 3′ UTR and inhibits TNF-α expression.•Gm4419 up-regulates TNF-α by targeting miR-466l.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0006-291XeISSN: 1090-2104DOI: 10.1016/j.bbrc.2017.07.021Titel-ID: cdi_proquest_miscellaneous_1917664903
- Format
- –
- Schlagworte
- Animals, Animals, Newborn, Apoptosis, Astrocytes - metabolism, Astrocytes - pathology, Base Sequence, bcl-2-Associated X Protein - genetics, bcl-2-Associated X Protein - metabolism, Binding Sites, Brain Injuries, Traumatic - genetics, Brain Injuries, Traumatic - metabolism, Brain Injuries, Traumatic - pathology, Caspase 3 - genetics, Caspase 3 - metabolism, Caspase 9 - genetics, Caspase 9 - metabolism, Cerebral Cortex - metabolism, Cerebral Cortex - pathology, Cyclin D1 - genetics, Cyclin D1 - metabolism, Gene Expression Regulation, Gm4419, LncRNA, Mice, Mice, Inbred C57BL, MicroRNAs - genetics, MicroRNAs - metabolism, Models, Biological, Neuroglia - metabolism, Neuroglia - pathology, Primary Cell Culture, Proto-Oncogene Proteins c-bcl-2 - genetics, Proto-Oncogene Proteins c-bcl-2 - metabolism, RNA, Long Noncoding - genetics, RNA, Long Noncoding - metabolism, Signal Transduction, Stress, Mechanical, Traumatic brain injury, Tumor necrosis factor α, Tumor Necrosis Factor-alpha - genetics, Tumor Necrosis Factor-alpha - metabolism