Knockdown of Circ_0003506 Impedes Radioresistance, Cell Growth, Migration and Invasion in Gastric Cancer.

BACKGROUND: Radioresistance is a major obstacle for clinical treatment of gastric cancer (GC). has_circ_0003506 (circ_0003506) was reported as an oncogenic factor in GC, but its effect on radioresistant GC is unclear. AIMS: This study aimed to explore the role of circ_0003506 in radioresistance and regulatory mechanism. METHODS: The expression detection was performed by real-time polymerase chain reaction. Cell survival was analyzed by colony formation assay. Cell proliferation was measured by Cell Counting Kit-8 assay and colony formation assay. Cell migration and invasion were examined using transwell assay. Cell apoptosis was assessed by flow cytometry. The target binding was confirmed via dual-luciferase reporter assay. The protein level was determined through western blot. Animal assay was performed for the functional exploration of circ_0003506 on radiosensitivity in vivo. RESULTS: Circ_0003506 was upregulated in radioresistant GC cells. Downregulation of circ_0003506 inhibited radioresistance to repress proliferation, migration and invasion but increase apoptosis in radioresistant GC cells. Circ_0003506 was a sponge of miR-1256. The effects of si-circ_0003506 on radioresistant GC cells were reverted by miR-1256 inhibitor. MiR-1256 suppressed tumor progression in radioresistant GC cells by downregulating bone morphogenetic protein type 2 receptor. Circ_0003506 regulated the level of bone morphogenetic protein type 2 receptor by targeting miR-1256. Downregulating circ_0003506 increased radiosensitivity of GC in vivo via regulating miR-1256 and bone morphogenetic protein type 2 receptor. CONCLUSION: Knockdown of circ_0003506 suppressed radioresistance in GC through the regulation of miR-1256/bone morphogenetic protein type 2 receptor axis. Circ_0003506 might be a therapeutic target in radiotherapy of GC.

circ_LRIG3 contributes to the progression of hepatocellular carcinoma by elevating RNF38 via sponging miR-449a.

Circular RNAs (circRNAs) play crucial roles in multiple cancers, including hepatocellular carcinoma (HCC). However, the effects and molecular mechanisms of circ_LRIG3 in HCC remain barely unknown. qRT-PCR assay was employed to detect the levels of circ_LRIG3, LRIG3, miR-449a and ring finger protein 38 (RNF38). RNase R assay and Actinomycin D assay were performed to analyze the characteristics of circ_LRIG3. Colony formation assay and MTT assay were used to evaluate cell proliferation. Flow cytometry analysis and transwell assay were adopted for cell apoptosis and metastasis, respectively. Western blot assay was carried out for the protein levels of Ki67, Snail, E-cadherin, RNF38, Smad2/3 and p-Smad2/3. Murine xenograft model assay was used to explore the role of circ_LRIG3 in vivo. circ_LRIG3 expression was upregulated in HCC tissues and cells. Knockdown of circ_LRIG3 suppressed proliferation, migration and invasion and facilitated cell apoptosis in HCC cells in vitro and blocked tumor growth of HCC in vivo. RNF38 overexpression reversed the effects of circ_LRIG3 knockdown on the malignant behaviors of HCC cells. Moreover, circ_LRIG3 could sponge miR-449a to positively modulate RNF38 expression in HCC cells. circ_LRIG3 knockdown inhibited the progression of HCC cells by sponging miR-449a. In addition, circ_LRIG3 silencing might inhibit the Smad2/3 pathway. circ_LRIG3 facilitated HCC progression by modulation of miR-449a/LRIG3 axis, which might provide a novel method for HCC therapy.

Corydaline alleviates Parkinson's disease by regulating autophagy and GSK-3ß phosphorylation.

BACKGROUND: Jitai tablet, a traditional Chinese medicine, has a neuroprotective effect on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mice. As one of the main active ingredients in the Jitai tablet, corydaline (Cory) has analgesic and anti-allergic effects, but it has not been studied in PD. Here, we investigated the role and mechanism of Cory in PD. METHODS: The PD model was induced by MPTP. Cell viability was measured by 3-(4, 5)-dimethylthiahiazo (-z-y1)-3, 5-di-phenytetrazoliumromide assay. The Pole test and traction test were performed to detect the behaviors of mice. The expression of tyrosine hydroxylase (Th) was detected by immunohistochemistry and Western blot. Immunofluorescence staining, monodansylcadaverine staining, and Western blot were conducted to assess autophagy. A lactic dehydrogenase release assay was used to detect cytotoxicity. Network pharmacology was used to screen the targets. RESULTS: There existed cytotoxicity when the concentration of Cory reached 40 µg/mL. Cory (not exceeding 20 µg/mL) could alleviate MPTP-induced cell damage. In vivo experiments indicated that Cory could improve the motor coordination of mice with PD. Besides, Cory could increase LC3-II/LC3-I levels both in vivo and in vitro. In addition, the Th levels reduced in the striatum and middle brain tissues of Parkinson's mice were recovered by Cory injection. We also found that Cory decreased the phosphorylation of glucogen synthase kinase-3 beta (GSK-3ß) at Tyr216 and increased the phosphorylation of GSK-3ß at Ser9 not only in primary neurons and SH-SY5Y cells but also in the striatum and middle brain tissues. Furthermore, Cory increased LC3-II/LC3-I levels and decreased p62 levels by regulating GSK-3ß. CONCLUSION: Cory enhanced autophagy, attenuated MPTP-induced cytotoxicity, and alleviated PD partly through the regulation of GSK-3ß phosphorylation.

Investigation of the electromagnetic characteristics and operating performance of a bidirectional PM excited machine.

This paper presents a study of bidirectional permanent magnet excited machine (BPMEM) based on the study of field-modulation permanent magnetic gear machine (FPGM). The BPMEM structure includes the installation of consequent-pole permanent magnets (PMs) on both the stator and rotor sides of the FPGM so that the stator and rotor can be bidirectionally excited to increase the working airgap flux density amplitude, reduce the flux leakage between poles, and increase the torque density. Therefore, the paper first analysis the influence of different airgap structures and PM arrangements on the airgap flux density and studies the winding slot-pole combination and the resulting working flux density harmonics to analyse the electromagnetic torque generation mechanism. By using the finite element analysis (FEA), the quantitative analysis and comparison of the FPGM, slot-wedge-less FPGM (SWL-FPGM), consequent-pole FPGM (CP-FPGM) and BPMEM verify the superiority of BPMEM in improving electromagnetic torque. In addition, the paper also studies the key performance of BPMEM's overload capacity, power factor and flux-weakening capability. Finally, no-load and independent load experiments are carried out on the FPGM prototype to verify the correctness of the FEA model and analysis method of the machine in this paper.

MicroRNA-552 Accelerates the Progression of Gastric Cancer by Targeting FOXO1 and Regulating PI3K/AKT Pathway.

The specific function of microRNA-552 (miR-552) has been investigated in several malignancies, except gastric cancer (GC). Therefore, this study was performed to determine the role of miR-552 in GC.GC tissues and adjacent non-tumor tissues were collected to determine the expressions of miR-552. Quantitative real-time polymerase chain reaction assays (RT-qPCR) and Western blot analysis were carried out to measure expression levels. The regulatory mechanism of miR-552 was explored by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) MTT Assay, and Transwell assays. The binding site between miR-552 and FOXO1 was verified by dual-luciferase reporter assays. Upregulation of miR-552 expression was detected and associated with worse clinical outcomes in GC. Furthermore, high miR-552 expression predicted poor prognosis in GC patients. Functionally, upregulation of miR-552 promoted cell viability, metastasis, epithelial-mesenchymal transition (EMT), and phosphatidylinositol 3-kinase and protein kinase B (PI3K/AKT) pathway in GC. In addition, miR-552 was confirmed to target forkhead box O1 (FOXO1) directly and inversely regulate its expression in GC. Upregulation of FOXO1 reversed the carcinogenesis of miR-552 in GC. In conclusion, miR-552 serves as a tumor promoter in GC through targeting FOXO1 and regulating EMT and PI3K/AKT pathway.