MALAT1 Activates the P53 Signaling Pathway by Regulating MDM2 to Promote Ischemic Stroke

Abstract

Background/Aims: This study focused on evaluating the effect of MALAT1 and MDM2 on ischemic stroke through regulation of the p53 signaling pathway. Materials: Bioinformatics analysis was performed to identify abnormally expressed lncRNAs, mRNAs and their associated pathways. Oxygen-glucose deprivation/reoxygenation (OGD/R) in cells and middle cerebral artery occlusion/reperfusion (MCAO/R) in mice were performed to simulate an ischemic stroke environment. Western blot and qRT-PCR were used to examine lncRNA expression and mRNA levels. Fluorescence in situ hybridization (FISH) LncRNA was used to locate mRNA. MTT and flow cytometry were performed to examine cell proliferation and apoptosis. Finally, immunohistochemistry was used to observe the expression of genes in vivo. Results: MALAT1 and MDM2, which exhibit strong expression in stroke tissues, were subjected to bioinformatics analysis, and the p53 pathway was chosen for further study. MALAT1, MDM2 and p53 signaling pathway-related proteins were all up regulated in OGD/R cells. Furthermore, Malat1, Mdm2 and p53 pathway related-proteins were also up regulated in MCAO/R mice. Both MALAT1 and MDM2 were localized in the nuclei. Down regulation of MALAT1 and MDM2 enhanced cell proliferation ability and reduced apoptosis, resulting in decreased infarct size in MCAO/R brains. Conclusion: These results indicate that MALAT1/MDM2/p53 signaling pathway axis may provide more effective clinical therapeutic strategy for patients with ischemic stroke.

LncRNA TPT1‐AS1 promotes tumorigenesis and metastasis in epithelial ovarian cancer by inducing TPT1 expression

“…Because siRNA mainly exert their gene‐silencing effects in cytoplasm, the RNA interference in nuclei does not seem as effective as in cytoplasm. However, in some studies, siRNA were utilized to silence lncRNA and mRNA expression in the nuclei, and the downstream genes and effects were efficaciously regulated . In our study, the TPT1‐AS1 depletion EOC cell lines were constructed by siRNA transfection, and were further utilized for in vitro function experiments.…”

“…However, in some studies, siRNA were utilized to silence lncRNA and mRNA expression in the nuclei, and the downstream genes and effects were efficaciously regulated. [41][42][43][44] In our study, the TPT1-AS1 depletion EOC cell lines were constructed by siRNA transfection, and were further utilized for in vitro function experiments. As the results showed, the knockdown efficiency of TPT1-AS1 was approximately 30%-40%, and the downregulation of TPT1-AS1 dramatically attenuated EOC cell proliferation, migration and invasion ability, and promoted cell adhesion ability, which are significantly opposite to the oncogenic effects of TPT1-AS1 overexpression.…”

The lncRNA Malat1 functions as a ceRNA to contribute to berberine-mediated inhibition of HMGB1 by sponging miR-181c-5p in poststroke inflammation

“…Malat1 was initially found to be upregulated in various tumor tissues and was thought to participate in the development and metastasis of cancer [ 14 ]. Subsequently, a clinical study demonstrated that Malat1 was highly expressed in ischemic stroke patients among the 20 studied lncRNAs [ 15 ]. In addition, increasing evidence has also indicated that Malat1 is significantly upregulated in microglia and neural cells to accelerate the inflammatory response in stroke [ 16 , 17 ].…”

LncRNAs Stand as Potent Biomarkers and Therapeutic Targets for Stroke

“…A mechanistic study showed that lncRNA-N1LR promoted neuroprotection likely through p53 phosphorylation inhibition (Wu et al, 2017). Another study demonstrated that lncRNA MALAT1 regulated MDM2 expression, further restrained the proliferation, and increased the apoptosis of OGD/R induced human BMECs via the p53 signaling pathway (Zhang et al, 2018).…”