The hsa_circRNA_102049 mediates the sorafenib sensitivity of hepatocellular carcinoma cells by regulating Reelin gene expression.

A growing body of research has illuminated that non-coding RNAs (ncRNAs) plays an important role in the development of drug resistance in hepatocellular carcinoma (HCC) cells. The expression profiles of differential expressed genes (DEGs) and ncRNAs related to the sorafenib resistance in HCC cells were analyzed according to the Gene Expression Omnibus (GEO) dataSets and The Cancer Genome Atlas (TCGA) datasets. Bioinformatics technology was used to construct the interaction network of DEGs and ncRNAs. Cell transfection, dual-luciferase reporter assay, Western blot, cell counting kit-8 (CCK-8), flow cytometry and quantitative real-time polymerase chain reaction(qRT-PCR) were used to study the mechanism of sorafenib resistance in HepG2 cells and Huh-7 cells. The expression of reelin (RELN) and secretagogin (SCGN) were the only down-regulated in sorafenib-resistant HCC cells. The results showed that RELN gene demethylation reversed the cytotoxic of sorafenib on HepG2 cells and Huh-7 cells. Hsa_circRNA_102049 over-expression promoted the sensitivity of HepG2 cells and Huh-7 cells to sorafenib, hsa_circRNA_102049 up-regulated the expression of RELN gene by sponging hsa-miR-214-3p. The resistance to sorafenib in RELN knockout HepG2 cells and Huh-7 cells could be reverted by has-circRNA_102049. These findings support targeting of hsa_circRNA_102049 and RELN in sorafenib-treated HCC cells as a novel intervention, which is expected to overcome sorafenib resistance of HCC cells.

Sevoflurane Postconditioning Ameliorates Neuronal Migration Disorder Through Reelin/Dab1 and Improves Long-term Cognition in Neonatal Rats After Hypoxic-Ischemic Injury.

Sevoflurane postconditioning (SPC) has been widely reported to attenuate brain injury after hypoxia-ischemia encephalopathy (HIE) by inhibiting neural necrosis and autophagy. Moreover, recent reports revealed that sevoflurane facilitated hippocampal reconstruction via regulating migration. Yet, it remains unclear whether the promotion of neural migration by SPC repairs the hippocampal injury after HIE. Here, we hypothesize that SPC exerts a neuroprotective effect by ameliorating neuronal migration disorder after HIE and regulating Reelin expression. Furthermore, the downstream Reelin/Dab1 pathway may be involved. The classical Rice-Vannucci model of hypoxia-ischemia was performed on postnatal day 7 rat pups, which was followed by SPC at 1 minimum alveolar concentration (MAC 2.5%) for 30 min. Piceatannol, causing Reelin aggregation in vivo, was used to detect whether Reelin/Dab1 was involved in the neuroprotection effect of SPC. Hippocampal-dependent learning ability tests were conducted to assess the long-term effects on locomotor activity and spatial learning ability. Our findings suggest that hypoxia-ischemia injury inhibited neurons migrated outward from the basal zone of dentate gyrus, disrupted cytoarchitecture of the dentate gyrus (DG), and led to long-term cognition deficits. However, SPC could relieve the restricted hippocampal neurons and repair the hippocampal-dependent memory function damaged after HIE by attenuating the overactivation of the Reelin/Dab1 pathway. These results demonstrate that SPC plays a pivotal role in ameliorating neuronal migration disorder and maintaining normal cytoarchitecture of the DG via inhibiting overactivated Reelin expression. This process may involve overactivated Reelin/Dab1 signaling pathway and spatial learning ability by regulating the Reelin expression which may associate with its neuroprotection.