HuR affects chemoresistance of small cell lung cancer by regulating FGFRL1 expression.

Human antigen R (HuR), an RNA-binding protein, has been demonstrated to serve an oncogenic role in various types of cancer. Fibroblast growth factor receptor-like 1 (FGFRL1) has been shown to regulate small cell lung cancer (SCLC) chemoresistance. In the present study, the role of HuR in chemoresistance of SCLC, as well as its possible molecular mechanism involving FGFRL1, was explored by reverse transcription-quantitative PCR, western blotting, Cell Counting Kit-8 assay, flow cytometry and RNA immunoprecipitation. The results revealed that HuR expression levels were markedly upregulated in drug-resistant SCLC cell lines (H69AR and H446DDP) compared with in the parental cell lines (H69 and H446). Knockdown of HuR in drug-resistant SCLC cells enhanced drug sensitivity, cell apoptosis and cell cycle arrest. Furthermore, molecular mechanism studies indicated that HuR could bind and regulate FGFRL1 expression levels to increase FGFRL1 mRNA stability. Taken together, the present study suggested that HuR may mediate chemoresistance of SCLC by regulating FGFRL1 expression. HuR may represent a prognostic predictor and a potential target for overcoming chemoresistance in SCLC.

Berberine Promotes Osteogenic Differentiation of Human Dental Pulp Stem Cells Through Activating EGFR-MAPK-Runx2 Pathways.

Similar to the mesenchymal stem cells (MSCs), dental pulp stem cells (DPSCs) also have pluripotent differentiation characteristic and may be more ideal for tissue regeneration, especially in tooth regeneration engineering. However, bacterial infection may be a powerful obstacle. Berberine (BBR), known with antibacterial effects, was recently found to play functions in bone formation through promoting osteogenic differentiation from pluripotent stem cells. However, whether BBR also function in DPSCs osteogenic differentiation has not yet been reported. Primary DPSCs were isolated from dental pulp tissues extracted from human impacted mandibular third molars, and identified by flow cytometry for cell surface antigen molecules. A dexamethasone osteogenic medium was used to induce DPSCs osteogenic differentiation. BBR (1 µM and 5 µM) was pre-added to into medium, and then cell proliferation, spheroid formation and osteogenic differentiation capacities of DPSCs were analyzed, as well as the underlying molecules modulation mechanism. Flow cytometry identified that CD44, CD90, CD81 and CD105 positively expressed in the isolated hDPSCs, with CD34 and CD45 negetively expressed. BBR enhanced the cell proliferation of hDPSCs in a dose-dependent pattern, and promoted dexamethasone-induced osteogenic differentiation via enhancing Runx2 transcription factor activity followed by upregulating osteogenesis markers expression, whereas the adipogenic differentiation of hDPSCs was suppressed dramatically by BBR. The EGFR and MAPK pathways were activated by BBR, and inhibitors for these pathways significantly suppressed the osteogenic differentiation promotion of BBR. These results have revealed a novel mechanism that berberine might promote hDPSCs osteogenic differentiation through activating EGFR-MAPK-Runx2 signaling pathways.

Complete sequence of a cholangiocarcinoma inbred Sprague-Dawley rat model mitochondrial genome.

In the present work we undertook the complete mitochondrial genome sequencing of an important cholangiocarcinoma model inbred rat strain for the first time. Its mitogenome was 16,312 bp and coding 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes. A total of 96 SNPs were examined when compared to reference BN sequence.

Immunohistochemical investigation of voltage-gated potassium channel-interacting protein 1 in normal rat brain and Pentylenettrazole-induced seizures.

Objective To explore the possible role of voltage-gated potassium channel-interacting protein 1 (KChIP1) in the pathogenesis of epilepsy. Methods Sprague Dawley female adult rats were treated with pentylenettrazole (PTZ) to develop acute and chronic epilepsy models. The approximate coronal sections of normal and epilepsy rat brain were processed for immunohistochemistry. Double-labeling confocal microscopy was used to determine the coexistence of KChIP1 and gamma-aminobutyric acid (GABA). Results KChIP1 was expressed abundantly throughout adult rat brain. KChIP1 is highly co-localize with GABA transmitter in hippocampus and cerebral cortex. In the acute PTZ-induced convulsive rats, the number of KChIP1-postive cells was significantly increased especially in the regions of CA1 and CA3 (P < 0.05); whereas the chronic PTZ-induced convulsive rats were found no changes. The number of GABA-labeled and co-labeled neurons in the hippocampus appeared to have no significant alteration responding to the epilepsy-genesis treatments. Conclusion KChIP1 might be involved in the PTZ-induced epileptogenesis process as a regulator to neuronal excitability through influencing the properties of potassium channels. KChIP1 is preferentially expressed in GABAergic neurons, but its changes did not couple with GABA in the epileptic models.