Targeting KRAS4A splicing through the RBM39/DCAF15 pathway inhibits cancer stem cells

The commonly mutated human KRAS oncogene encodes two distinct KRAS4A and KRAS4B proteins generated by differential splicing. We demonstrate here that coordinated regulation of both isoforms through control of splicing is essential for development of Kras mutant tumors. The minor KRAS4A isoform is enriched in cancer stem-like cells, where it responds to hypoxia, while the major KRAS4B is induced by ER stress. KRAS4A splicing is controlled by the DCAF15/RBM39 pathway, and deletion of KRAS4A or pharmacological inhibition of RBM39 using Indisulam leads to inhibition of cancer stem cells. Our data identify existing clinical drugs that target KRAS4A splicing, and suggest that levels of the minor KRAS4A isoform in human tumors can be a biomarker of sensitivity to some existing cancer therapeutics.

Tripartite Coordinated Regulation of New Energy Vehicles Based on Dynamic Bayesian Game

Manufacturers are disseminating false or ambiguous information regarding new energy vehicles (NEVs), which has led to skepticism from consumers about the quality of NEVs. In this research, we simultaneously considered the relationship among manufacturers, consumers, and governments from the perspective of stakeholders, and then we analyzed the tripartite coordinated regulation. In view of the serious information asymmetry of NEVs, we innovatively developed the Bayesian dynamic game model. By solving refined Bayesian equilibrium strategies, this study explores the effects of key influencing factors on strategic choices. On the basis of the conclusion, relevant countermeasures and suggestions are put forward to engender effective regulation by governments.