LINC02308 promotes the progression of glioma through activating mTOR/AKT-signaling pathway by targeting miR-30e-3p/TM4SF1 axis.

BACKGROUND: Glioma is a common brain malignancy, and the purpose of this study is to investigate the function of LINC02308 in glioma. METHODS: The differentially expressed lncRNAs were screened by microarray. The expression of LINC02308 in glioma tissues and cells was evaluated. The interaction among LINC02308, miR-30e-3p, and TM4SF1 was determined. Cell proliferation and apoptosis were evaluated. The expression of mTOR/AKT-signaling and apoptosis-related markers was detected by Western blot. A xenograft tumor mouse model was constructed to investigate the roles of LINC02308. RESULTS: LINC02308 was significantly overexpressed in glioma, and a high LINC02308 level was correlated with a poor prognosis. LINC02308 silencing markedly inhibited proliferation and reduced apoptosis of glioma cells and also suppressed tumor growth in the xenograft tumor mouse model. Finally, we demonstrated that LINC02308 played its oncogenic role through binding to miR-30e-3p so as to relieve miR-30e-3p-induced suppression of TM4SF1. CONCLUSIONS: LINC02308 promoted glioma tumorigenesis as a sponge of miR-30e-3p to upregulate TM4SF1 and activate AKT/mTOR pathway. Graphical Abstract Hypothesis diagram illustrates the function and mechanism of LINC02308 in glioma. A schematic representation of the functional mechanism of LINC02308 in glioma.

Effect of TrkB-PLC/IP3 pathway on intestinal inflammatory factors and enterocyte apoptosis in mice with colitis.

In this study, we aimed to explore the effect of TrkB-PLC/IP3 pathway on intestinal inflammatory factors and enterocyte apoptosis in mice with colitis. The mouse model of ulcerative colitis was established by medication, and 40 SPF C57BL/6J mice (8 weeks old) were randomly divided into normal group (healthy mice, n = 10), control group (sham-operated mice, n = 10), model group (model mice without any treatment, n = 10), and K252a group (model mice treated with 100 µmol/kg TrkB-PLC/IP3 pathway inhibitor for 5 days before clysis, n = 10). The results showed that mice in the model and K252a groups, as compared with normal and control groups, had no significant changes in the levels and protein expressions of serum tumor necrosis factor-α (TNF-α) and TNF-γ in the colon tissues (P>0.05), and had a significant increase in disease activity index, colon mucosa damage index, tissue damage index scores, and levels and protein expressions of serum interleukin-4 (IL-4) and IL-8, but had a significant decrease in the level and protein expression of serum IL-10 (P<0.05). Mice in the model and K252a groups showed blocked enterocyte cycle progression, elevated apoptosis ratio, and significantly increased mRNA and protein expressions of Caspase3, Bax, FasL, and Fas, but significantly reduced mRNA and protein expressions of p-TrkB, PLC-γ1, IP3, and Bcl-2 (P<0.05). Moreover, intestinal inflammation and apoptosis induced by colitis in the K252a group became more aggravated by inhibiting the activity of TrkB-PLC/IP3 pathway. In conclusion, inhibition of TrkB-PLC/IP3 pathway can increase the expression of intestinal inflammatory factors and promote enterocyte apoptosis in mice with colitis.

LncRNA TPT1-AS1 Sponges miR-23a-5p in Glioblastoma to Promote Cancer Cell Proliferation.

Background: Long noncoding RNA (LncRNA) TPT1-AS1 is an oncogene in ovarian cancer and cervical cancer, while its role in glioblastoma (GBM) is unknown. The bioinformatics analysis in this study showed that miR-23a-5p may bind to TPT1-AS1. This study was performed to investigate the interactions between miR-23a-5p and TPT1-AS1 in GBM. Materials and Methods: A total of 60 GBM patients (40 males and 20 females, 24 to 60 years old, mean age 41.7 ± 7.8 years old) were enrolled at the First Hospital of Jilin University between April 2016 and April 2018. Gene expression levels were determined by qPCR and Western blot. Cell transfections were performed to analyze the interactions between TPT1-AS1, miR-23a-5p, and extracellular matrix protein 1 (ECM1). Cell proliferation was detected by cell proliferation assay. Results: The authors found miR-23a-5p was downregulated in GBM and TPT1-AS1 was upregulated in GBM, whereas the expression of these two was not significantly correlated. In GBM cells, overexpression of TPT1-AS1 did not affect the expression of miR-23a-5p, but upregulated ECM1. In cell proliferation assay, overexpression of TPT1-AS1 and ECM1 resulted in increased proliferation rate of GBM cells. Overexpression of miR-23a-5p attenuated the effects of overexpressing TPT1-AS1. Conclusions: TPT1-AS1 may sponge miR-23a-5p in GBM to promote cancer cell proliferation by upregulating ECM1.

Berberine promotes nerve regeneration through IGFR­mediated JNK­AKT signal pathway.

Berberine presents therapeutic ability for various central nervous system disorders, including Alzheimer's disease and cerebral ischemia. The present study investigated the role of berberine in nerve regeneration and analyzed the potential mechanism mediated by berberine in hippocampal pyramidal neurons. Reverse transcription­quantitative poylmerase chain reaction, western blot, TUNEL assay and immunofluorescence were used to analyze the therapeutic effects of berberine on nerve regeneration. Berberine treatment increased growth and viability of hippocampal pyramidal neurons. Berberine treatment inhibited apoptosis of hippocampal pyramidal neurons and increased apoptosis regulator Bcl­2 and Bcl­w expression. Neuroinflammation of tumor necrosis factor α, interleukin (IL)1ß, IL6 levels and autophagy­related proteins microtubule­associated proteins 1A/1B light chain 3B, autophagy related 16 like 1 and autophagy related 7 were downregulated by berberine treatment in hippocampal pyramidal neurons. Notably, study has found that berberine increased insulin-like growth factor receptor (IGFR) and decreased c­Jun N­terminal kinase (JNK) and protein kinase B (AKT) expression in hippocampal pyramidal neurons. IGFR antagonist abolished berberine­increased growth of hippocampal pyramidal neurons. In conclusion, these results indicate that berberine can promote nerve regeneration through IGFR­mediated JNK­AKT signal pathway.