The lncRNA-AK046375 Upregulates Metallothionein-2 by Sequestering miR-491-5p to Relieve the Brain Oxidative Stress Burden after Traumatic Brain Injury

Abstract

We previously discovered that traumatic brain injury (TBI) induces significant perturbations in long noncoding RNA (lncRNA) levels in the mouse cerebral cortex, and lncRNA-AK046375 is one of the most significantly changed lncRNAs after TBI. lncRNA-AK046375 overexpression and knockdown models were successfully constructed both in vitro and in vivo. In cultured primary cortical neurons and astrocytes, lncRNA-AK046375 sequestered miR-491-5p, thereby enhancing the expression of metallothionein-2 (MT2), which ameliorated oxidative-induced cell injury. In addition, upregulated lncRNA-AK046375 promoted the recovery of motor, learning, and memory functions after TBI in C57BL/6 mice, and the underlying mechanism may be related to ameliorated apoptosis, inhibited oxidative stress, reduced brain edema, and relieved loss of tight junction proteins at the blood-brain barrier in the mouse brain. Therefore, we conclude that lncRNA-AK046375 enhances MT2 expression by sequestering miR-491-5p, ultimately strengthening antioxidant activity, which ameliorates neurological deficits post-TBI.

Single-cell RNA-seq reveals cellular heterogeneity from deep fascia in patients with acute compartment syndrome

“…These nine subpopulations of T cells, especially Tregs, may be involved in protecting apoptosis and suppressing proinflammatory cytokines under high stress, which provides a novel insight into the treatment of ACS. In contrast, the MT family, which was found to have a role in the reduction of oxidative damage and apoptosis in animal models and was involved in the binding of a large number of heavy metal ions such as zinc ions, copper ions, or cadmium ions ( 58 , 59 ), was down-regulated in nine subsets ( 60 – 62 ). We suppose that HSP , MT , or the ratio of HSP to MT may be an important disease biomarker in the diagnosis of ACS, or maybe a potential key factor of ACS that is worthy of study at the protein level.…”

LncRNA FRMD6‐AS1/miR‐491‐5p/USP13 pathway attenuated ferroptosis and contributed to liver fibrosis

“…In this study, lncRNA FRMD6-AS1 expression was elevated in activated HSC-T6 cells, and knockdown of FRMD6-AS1 increased iron miR-491-5p can be declined by lncRNAs in cancers, brain oxidative stress after brain injury, and atherosclerosis. 41,42 By competitively binding with miR-491-5p, lncRNAs, such as lncRNA AK046375, LINC02381 and lncRNA LBX2-AS1, can modulate the progression cancers and oxidative stress. 41,42 In addition, miR-491-5p exerts Several target genes of miR-491-5p, including emilin 1, TP53 and metallothionein-2, could be dramatically repressed by miR-491-5p via binding to 3' UTRs.…”

Characterization of the lncRNA-miRNA-mRNA regulatory network to reveal potential functional competing endogenous RNAs in traumatic brain injury

“…Actually, the main ways of lncRNAs on regulating the expressions of mRNAs through influencing the expression and/or chromatin state of nearby genes and interacting with proteins and/or other RNA molecules such as miRNAs ( Marchese et al, 2017 ). Recent study have revealed that downregulation of miR-491-5p promotes neovascularization after TBI ( Tang et al, 2022b ), and lncRNA-AK046375 enhances MT2 expression by sequestering miR-491-5p, ultimately strengthening antioxidant activity, which ameliorates neurological deficits post-TBI ( Tang et al, 2022a ). These studies show the prospect of ceRNA regulation mechanism in TBI research.…”