Circular RNA circ_0000950 promotes neuron apoptosis, suppresses neurite outgrowth and elevates inflammatory cytokines levels via directly sponging miR-103 in Alzheimer’s disease

Abstract

This study aimed to investigate the effect of circ_0000950/miR-103 network on regulating neuron apoptosis, neurite outgrowth and inflammation in Alzheimer's disease (AD). Cellular AD model of rat pheochromocytoma cell line PC12 cells and cellular AD model of rat cerebral cortex neurons were constructed, and the effect of circ_0000950 on apoptosis, neurite outgrowth and inflammation in both cellular AD models was determined through upregulation and knockdown of circ_0000950 expression by transfection. Compensation experiments and luciferase assay were further performed to validate the sponging effect of circ_0000950 on miR-103 as well as the mechanisms of circ_0000950/miR-103 on regulating apoptosis, neurite outgrowth and inflammation in both cellular AD models. Circ_0000950 reduced miR-103 expression and increased prostaglandin-endoperoxide synthase 2 (PTGS2) expression in both two cellular AD models. And circ_0000950 overexpression promoted neuron apoptosis, suppressed neurite outgrowth and elevated IL-1β, IL-6 and TNF-α levels compared with overexpression control, whereas circ_0000950 knockdown inhibited neuron apoptosis, enhanced neurite outgrowth and lowered IL-1β, IL-6 and TNF-α levels compared with shRNA control in both two cellular AD models. Compensation experiments along with luciferase reporter assay validated that circ_0000950 promoted cell apoptosis, suppressed neurite outgrowth and elevated inflammatory cytokines levels via directly sponging miR-103. In conclusion, circ_0000950 promotes neuron apoptosis, suppresses neurite outgrowth and elevates inflammatory cytokines levels through directly sponging miR-103 in AD.

Diagnostic Value of miR-103 in Patients with Sepsis and Noninfectious SIRS and Its Regulatory Role in LPS-Induced Inflammatory Response by Targeting TLR4

“…Previous studies have showed that miR-103 plays an important regulatory role in inflammatory responses, such as the inhibiting effect of miR-103 on inflammation in obesity and metabolic syndrome-related disorders [29], chronic obstructive pulmonary disease [30], and Alzheimer's disease [15]. In the present study, the serum miR-103 was found to be negatively correlated with inflammatory cytokine levels in sepsis patients.…”

“…In this study, we found a complementary sequence of miR-103 at the 3′-untranslated region (3′-UTR) of TLR4. Previous studies have demonstrated the regulatory effects of miR-103 on inflammatory responses in some human diseases, such as Alzheimer's disease [15] and atherosclerosis [16]. Of note, a study by Huang et al investigated the miRNA expression profiles in neonatal sepsis using neonatal monocytes, which are key leukocytes that link innate to adaptive immunity, and found that miR-103 was decreased in LPS-treated cells [17].…”

Epigenetics: Recent Advances and Its Role in the Treatment of Alzheimer's Disease

“…CircRNA KIAA1586 is significantly enriched in AD-associated biological processes and may be a novel risk factor in the pathogenesis of AD (138). CircRNA circ_0000950 promotes neuron apoptosis, inhibits the production of neurite outgrowth, and increases the levels of inflammatory cytokine levels via sponging microRNA-103 in AD (139). CircNF1-419 upregulates autophagy and reduces Aβ and tau expression by binding the proteins Dynamin-1 and adaptor protein 2 B1 (140).…”

“…Neuronal (N2a) and fibroblastic (NIH 3T3) cells MicroRNA-298 and microRNA-328 were associated with BACE1 (118) circRNA circ_0000950 Cellular AD model Circ_0000950 promoted neuron apoptosis, inhibited the production of neurite outgrowth, and increased the levels of inflammatory cytokines levels (139) circRNA CircNF1-419 SD rat model CircNF1-419 upregulated autophagy and reduced Aβ and tau (140) circRNA, circular RNA; BACE1-AS, BACE1-antisense transcript; SOX21-AS1, SOX21 antisense RNA 1; NEAT1, Nuclear paraspeckle assembly transcript 1.…”

“…The mechanisms underlying epigenetic regulation of non-coding RNAs in AD are complex. As we mention, circRNAs mediate the effect of microRNAs ( 139 ). MicroRNAs are regulated by chromatin modifications and DNA methylation, which are implicated in AD by targeting messenger RNA (mRNA) expression ( 182 ).…”