[Interference of Lumican Regulates the Invasion and Migration of Liver Cancer Cells].

OBJECTIVE: To explore the effect of silencing lumican on the invasion and migration of liver cancer cells. METHODS: Lumican was silenced by shRNA in liver cancer cells (HepG2 and MHCC97H). The mRNA levels of lumican were detected by qRT-PCR. Cell invasion was measured by Transwell. Cell migration was tested via wound healing. The protein levels of lumican,MMP-9,VEGF,ERK1,JNK,p-ERK1 and p-JNK were measured by Western blot. RESULTS: Liver cancer cells (HepG2 and MHCC97H) had higher levels of mRNA and protein of lumican compared with normal hepatocyte L02 (P<0.01). shRNA lowered the levels of mRNA and protein of lumican (P<0.01),and weakened the invasion and migration of cancer cells (P<0.01). The expressions of MMP-9 and VEGF decreased with the shRNA silence (P<0.01). shRNA also reduced the protein level of p-ERK1 and p-JNK (P<0.01). CONCLUSION: Silencing lumican by shRNA attenuates the invasion and migration of liver cancer cells via inhibiting the activation of ERK1/JNK pathway.

Design and Synthesis of Functionally Active 5-Amino-6-Aryl Pyrrolopyrimidine Inhibitors of Hematopoietic Progenitor Kinase 1.

Immune activating agents represent a valuable class of therapeutics for the treatment of cancer. An area of active research is expanding the types of these therapeutics that are available to patients via targeting new biological mechanisms. Hematopoietic progenitor kinase 1 (HPK1) is a negative regulator of immune signaling and a target of high interest for the treatment of cancer. Herein, we present the discovery and optimization of novel amino-6-aryl pyrrolopyrimidine inhibitors of HPK1 starting from hits identified via virtual screening. Key components of this discovery effort were structure-based drug design aided by analyses of normalized B-factors and optimization of lipophilic efficiency.

Exosome-Derived Circ-PVT1 Contributes to Cisplatin Resistance by Regulating Autophagy, Invasion, and Apoptosis Via miR-30a-5p/YAP1 Axis in Gastric Cancer Cells.

Background: Emerging studies manifested that exosomal RNAs had pivotal roles in human cancer therapies. This article aimed to research the regulatory mechanism of exosomal circRNA-plasmacytoma variant translocation 1 (circ-PVT1) in cisplatin (DDP) resistance of gastric cancer (GC). Methods: Exosomes were isolated by ExoQuick® method and ultracentrifugation and then identified through transmission electron microscope and the examination of exosome markers. Related proteins were detected using Western blot. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied for measuring circ-PVT1, microRNA-30a-5p (miR-30a-5p), and Yes-associated protein 1 (YAP1) expression. The half inhibitory concentration (IC50) of DDP was assessed by 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT). Cell apoptosis and invasion were, respectively, determined using flow cytometry and transwell assay. Target relationship was confirmed by dual-luciferase reporter assay. The impact of circ-PVT1 on DDP resistance was explored via xenograft tumor assay. Results: Exosomal circ-PVT1 was upregulated while miR-30a-5p was downregulated in DDP-resistant GC serums and cells. Circ-PVT1 knockdown repressed DDP resistance in DDP-resistant GC cells via promoting apoptosis and decreasing invasion or autophagy by negatively targeting miR-30a-5p. YAP1 was a direct target of miR-30a-5p. MiR-30a-5p overexpression inhibited DDP resistance via reducing YAP1. Circ-PVT1 modulated YAP1 expression by targeting miR-30a-5p. Circ-PVT1 depression expedited DDP sensitivity of GC via miR-30a-5p/YAP1 axis in vivo. Conclusion: Exosomal circ-PVT1 facilitated DDP resistance via modulating autophagy, invasion and apoptosis by miR-30a-5p/YAP1 axis in GC cells. Exosomal circ-PVT1 might be a prospective indicator in DDP therapy of GC.

Novel Z-scheme W18O49/CeO2 heterojunction for improved photocatalytic hydrogen evolution.

The novel Z-scheme heterojunction photocatalyst W18O49/CeO2 was prepared by hydrothermal synthesis. The photocatalytic properties of W18O49/CeO2 were evaluated by photocatalytic hydrogen evolution under visible light. The result shows that the 15 wt% W18O49/CeO2 composite has the best hydrogen production efficiency of about 0.2061 mmol g-1h-1, which was 1.93 times higher than that the obtained pure CeO2. The characterization results demonstrated that the existence of Z-scheme heterojunction structure at the contact interface of W18O49 and CeO2 was the origin of the enhanced photocatalytic performance for hydrogen evolution, which could greatly increase the accumulation of photo-generated electrons and the separation efficiency of charge carrier. In accordance with density functional theory (DFT) calculation, we further confirmed the formation of Z-scheme heterojunction structures. This work is anticipated to expand the ideas for modifying CeO2 semiconductor materials to improve the rate of photocatalytic hydrogen production.