Dependence of artesunate on long noncoding RNA-RP11 to inhibit epithelial-mesenchymal transition of hepatocellular carcinoma.

As a first line medicine for malaria treatment, artesunate (ART) also shows antitumor potential. However, little is known about the effect of ART on the cancer cell epithelial-mesenchymal transition (EMT). In this study, we found that ART inhibited cell growth in SK-HEP1 and SM7721 hepatocellular carcinoma cell lines. A microarray was used to identify differentially expressed protein-coding RNAs (pcRNA) and long noncoding RNAs (lncRNA) between SK-HEP1 cells with and without ART treatment. A differentially expressed lncRNA-RP11, the most related to the EMT of liver cancer cells-RP11 was identified by abioinformatics method Overexpressing and silencing assays were used to verify the role of RP11 in cancer cell EMT. The levels of RP11- and EMT-related genes in liver cancer samples from 75 patients were detected by using qualitative polymerase chain reaction or immunohistochemistry. We identified 1334 pcRNAs and 1670 lncRNA with differential expression induced by ART. ART inhibits EMT, proliferation, migration, invasion, and adhesion of liver cancer cells. RP11 depresses the inhibitory effect of ART on cancer cell EMT. The level of RP11 is associated with cancer cell EMT and metastasis and survival rate of the patient. These data suggest that RP11-linking ART and cancer cell EMT are important for ART-inhibited metastasis of liver cancer.

ESAT6 inhibits autophagy flux and promotes BCG proliferation through MTOR.

In recent years, increasing studies have found that pathogenic Mycobacterium tuberculosis (Mtb) inhibits autophagy, which mediates the anti-mycobacterial response, but the mechanism is not clear. We previously reported that secretory acid phosphatase (SapM) of Mtb can negatively regulate autophagy flux. Recently, another virulence factor of Mtb, early secretory antigenic target 6 (ESAT6), has been found to be involved in inhibiting autophagy, but the mechanism remains unclear. In this study, we show that ESAT6 hampers autophagy flux to boost bacillus Calmette-Guerin (BCG) proliferation and reveals a mechanism by which ESAT6 blocks autophagosome-lysosome fusion in a mammalian target of rapamycin (MTOR)-dependent manner. In both Raw264.7 cells and primary macrophages derived from the murine abdominal cavity (ACM), ESAT6 repressed autophagy flux by interfering with the autophagosome-lysosome fusion, which resulted in an increased load of BCG. Impaired degradation of LC3Ⅱ and SQSTM1 by ESAT6 was related to the upregulated activity of MTOR. Contrarily, inhibiting MTOR with Torin1 removed the ESAT6-induced autophagy block and lysosome dysfunction. Furthermore, in both Raw264.7 and ACM cells, MTOR inhibition significantly suppressed the survival of BCG. In conclusion, our study highlights how ESAT6 blocks autophagy and promotes BCG survival in a way that activates MTOR.

Effect of PSMA7 on RB pathway in A549 cells / 中国免疫学杂志

Objective:To investigate the effect of upregulated and downregulated PSMA7 on the cell cycle and Cyclin D1,CDK4,P16,Rb of RB pathway in A549 cells.Methods:Transfected upregulated pcDNA3.1-PSMA7 vecter and downregulated pGPU6/Hygro-PSMA7-265 vecter into A549 cells,and then tested the effect of PSMA7 on the cell cycle of A549 cells by flow cytometry,and detected the protein level of Cyclin D1,CDK4,P16,Rb by Western blot.Results:Compared with the control group,the cell cycle of the A549 cells did not change significantly,and the expression of Cyclin D1,CDK4 decreased but P16,Rb increased when PSMA7 was upregulated.Compared with the control group,the proportion of phase G0/G1,G2/M of the A549 cells decreased and phase S increased,and the expression of Cyclin D1,CDK4 increased but P16,Rb decreased when PSMA7 was downregulated.There was statistical significance for those results.Conclusion:PSMA7 could affect the expression of Cyclin D1,CDK4,P16,Rb protein level of RB pathway in A549 and promoted the A549 cells into phase S when it′s downregulated.

Effect of low density lipoprotein and oxidized low density lipoprotein on the secretion of endothelin in endothelial cells / 中国康复理论与实践

@#ObjectiveTo investigate the effect of low density lipoprotein(LDL) and oxidized low density lipoprotein(ox-LDL) on the secretion of endothelin(ET) and whether LDL to be oxidized and modified by ox-LDL in vitro.MethodsEndothelial cell strain ECV-304 was incubated with different concentration of LDL(50 and 100 mg/L),ox-LDL(50 and 100 mg/L) or LDL+ox-LDL(50mg/L) for 24 hours,then cells and cultured medium were collected.ET in cells and cultured medium were detected with radioimmunoassay.ResultsBoth of LDL and ox-LDL enhanced the secretion of ET in cultured endothelial cells;the effect of ox-LDL was more markedly than LDL.LDL+ox-LDL had a greater effect than any of the two lipoproteins alone.ConclusionLDL and ox-LDL may have the ability to promote the secretion of ET in cultured endothelial cells and LDL can be oxidized and modified by ox-LDL in vitro.