Influence of lncRNA-MALAT1 on neuronal apoptosis in rats with cerebral infarction through regulating the ERK/MAPK signaling pathway.

OBJECTIVE: To investigate the regulatory effect of long non-coding ribonucleic acid (lncRNA)-metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway, and to explore its influence on neuronal apoptosis in rats with cerebral infarction.
MATERIALS AND METHODS: A total of 45 adult male Sprague-Dawley rats were randomly divided into sham group (n=15), model group (n=15) and MALAT1 low-expression group (n=15). The model of cerebral infarction was successfully established in the model group and MALAT1 low-expression group via middle cerebral artery occlusion (MCAO). After 3 d, the nerve injury in each group was evaluated using Zea-Longa score. Meanwhile, the area of cerebral infarction in each group was detected via 2,3,5-triphenyl tetrazolium chloride (TTC) staining. After the cortical tissues were separated, the expression level of lncRNA-MALAT1 was detected via quantitative Polymerase Chain Reaction (qPCR). The apoptotic level of neurons in each group was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The expression levels of inflammatory factors were detected using enzyme-linked immunosorbent assay (ELISA) kits. Furthermore, the expression levels of apoptosis-related proteins and ERK/MAPK signaling pathway-related proteins were detected via Western blotting.
RESULTS: Compared with the sham group, the behavioral score and area of cerebral infarction in the model group were significantly increased (p<0.01). The low expression of MALAT1 could effectively reduce the behavioral score and area of cerebral infarction in the model group (p<0.01). The expression level of lncRNA-MALAT1 in cortical tissues of the model group was markedly higher than that of the sham group and MALAT1 low-expression group (p<0.01). Compared with the sham group, the content of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cortical tissues was significantly increased (p<0.01). However, the content of IL-10 was remarkably decreased in the model group (p<0.01). Low expressed MALAT1 could markedly reduce the content of TNF-α and IL-6 and increase the content of IL-10 in cortical tissues (p<0.01). The level of apoptosis in cortical tissues was increased in the model group when compared with that of the sham group (p<0.01). Meanwhile, low expression of MALAT1 could effectively reduce the apoptosis level in cortical tissues in model group (p<0.01). In the model group, the expression levels of B-cell lymphoma-2/Bcl-2 associated X protein (Bcl-2/Bax), p-ERK and matrix metalloproteinase-2 (MMP-2) in cortical tissues were significantly declined than the sham group (p<0.01). However, the protein expression level of cleaved caspase-3 was markedly increased (p<0.01). Furthermore, the low expression of MALAT1 could remarkably increase the expressions of Bcl-2/Bax, p-ERK and MMP-2 (p<0.01), as well as decrease the expression of cleaved caspase-3 (p<0.01).
CONCLUSIONS: LncRNA-MALAT1 may increase the release of inflammatory cytokines by inhibiting the ERK/MAPK signaling pathway, thereby up-regulating the level of neuronal apoptosis and aggravating the cerebral injury in rats with cerebral infarction.