Hippocampal sclerosis (HS) is one of the most common pathological type of intractable temporal lobe epilepsy (TLE), often characterized by hippocampal atrophy, neuronal apoptosis, and gliogenesis. However, the molecular mechanisms of neuronal apoptosis in patients with HS are still not fully understood. We therefore conducted a pilot study focusing on the neuronal apoptosis ceRNA network in the sclerotic hippocampus of intractable TLE patients. In this research, RNA sequencing (RNA-seq) was utilized to quantify the expression levels of lncRNAs, miRNAs, and mRNAs in TLE patients with HS (HS-TLE) and without HS (non-HS-TLE), and reverse transcription-quantitative PCR (qRT-PCR). The interactions of differential expression (DE) lncRNAs-miRNAs or DEmiRNAs-mRNAs were integrated by StarBase v3.0, and visualized using Cytoscape. Subsequently, we annotate the functions of lncRNA-associated competitive endogenous RNA (ceRNA) network through analysis of their interactions with mRNAs. RNA-seq analyses showed 381 lncRNAs, 42 miRNAs, and 457 mRNAs were dysregulated expression in HS-TLE compared to non-HS-TLE. According to the ceRNA hypothesis, 5 HS-specific ceRNA network were constructed. Among them, the core ceRNA regulatory network involved in neuronal apoptosis was constituted by 10 DElncRNAs (CDKN2B-AS1, MEG3, UBA6-AS1, etc.), 7 DEmiRNAs (hsa-miR-155-5p, hsa-miR-195-5p, hsa-miR-200c-3p, etc.), and 3 DEmRNAs (SCN2A, DYRK2, and MAPK8), which belonging to apoptotic and epileptic terms. Our findings established the first ceRNA network of lncRNA-mediated neuronal apoptosis in HS-TLE based on transcriptome sequencing, which provide a new perspective on the disease pathogenesis and precise treatments of HS.
Postoperative neurocognitive disorder (PND) is one of the most common postoperative neurological complications in aged patients, characterized by mental disorder, anxiety, personality changes, and impaired memory. At present, the molecular mechanism of PND remains largely unclear, and the ideal biomarker for clinical diagnosis and prognosis are lacking. Circular RNA (circRNA) and microRNA (miRNA), as unique non-coding RNAs, affecting the regulation of miRNAs on genes and further intervening in the progression of diseases through the sponge action between the two. Besides, it could be served as novel biomarkers in various diseases. In order to detect the differential expression profiles of genes caused by PND, a total of 26 18-month-old male C57BL/6 mice were randomly assigned to control group and PND group. Behavioral tests showed that mice in the PND group had impaired cognitive function compared with the control group. Three mice in each group were randomly selected to harvest the brain for analysis the expressions of circRNAs, miRNAs, and mRNAs in the prefrontal cortex by next-generation sequencing (NGS) technology. Differentially expressed genes, including 1192 circRNAs, 27 miRNAs, and 266 mRNAs were identified, and its accuracy was further confirmed by qRT-PCR. Bioinformatics analysis results suggested that neuroinflammation was the main pathological mechanism of PND. The construction of competitive endogenous RNA (ceRNA) networks and the identification of hub genes provided possible therapeutic targets for PND. Cinnarizine and Clemastine were predicted to have the potential therapeutic effects on PND. This is the first study to explore the differential expression profiles of genes and their regulation mechanisms in PND, our results provided new clues and targets for the treatment of this refractory disease.