Downregulation of lncRNA KCNQ1OT1 relieves traumatic brain injury induced neurological deficits via promoting "M2" microglia polarization.

Background: Microglia-induced neuroinflammation is one of the main characteristics of traumatic brain injury (TBI). Presently, we aim to investigate the role of long non-coding RNA (lncRNA) KCNQ1 overlapping transcript 1 (KCNQ1OT1) in TBI-induced neurological deficits and the related mechanism.

Methods: An in-vivo TBI model was established in mice, and in-vitro experiments were carried out on BV2 microglia. Then the neurological functions, microglial activation, inflammatory cytokines, and proteins were detected.

Results: Our data indicated that KCNQ1OT1 was markedly overexpressed in the cerebral tissues of TBI mice, accompanied by a higher level of the cytokines (including IL-1β, IL-6, and TNFα). However, knocking down KCNQ1OT1 relieved neurological deficits, neuron loss, and blood-brain barrier damage. Besides, overexpressing miR-873-5p enhanced the "M2″ polarization of microglia by repressing the TRAF6-mediated p38 and NF-κB pathways. In contrast, downregulating KCNQ1OT1 repressed microglial neuroinflammation by attenuating the "M1″ polarization of microglia and promoting "M2″ polarization of microglia, and inactivating the p38 and NF-κB pathway.

Conclusions: Mechanistically, KCNQ1OT1 functioned as a competitive endogenous RNA (ceRNA) by sponging miR-873-5p, which targeted the 3' untranslated region (UTR) of TRAF6. Overall, our data confirmed that downregulating lncRNA KCNQ1OT1 exerted neuroprotective effects on TBI mice by modulating the miR-873-5p-TRAF6-p38/NF-κB axis.