| The Hippo pathway is an evolutionarily conserved key regulator of organ size.More importantly,deregulation of the Hippo pathway leads to human cancers.The Hippo pathway mainly functions by inhibiting a transcription co-activator called YAP.However,not all key target genes of YAP in vivo have been identified and the potency of the Hippo pathway remains unexplained.We found that YAP induces a microRNA,miR-130a,which targets a YAP inhibitor,VGLL4,thus forms a positive feedback loop,which sustains strong activity of the Hippo pathway.Meanwhile,we proved that the inhibition of miR-130a dampened Hippo pathway output and reversed organ size enlargement and tumorigenesis induced by Hippo pathway deregulation or YAP activation.Hepatocellular carcinoma(HCC)poses a threat to human health worldwide,especially in China,where the incidence,mortality,and prevalence of HCC are particularly severe.However,liver resection and liver transplantation are only suitable for a small number of people and effective therapeutic drug is lacking.The liver is an important organ for glycogen synthesis and storage and stability of blood glucose level.However,the mechanism of liver tumor metabolism,especially glucose metabolism,is still poorly understood.We combined the hydrodynamic injections with transposon to achieve stabIe expression of oncogenes to establish mouse models better resemble human liver cancer.On the basis of the mouse model,we explored the expression change of pyruvate kinase,a key enzyme in glucose metabolism,and found that PKM2 expression was increased in most tumors,and most of them were accompanied by an increase in PKM1.In addition,only 4%of the tumors had a potential PKM2 and PKM1 isoform switch.We hope to further explore the effect of PKM2 on the occurrence of HCC,not only to solve the controversial problem of PKM2 function in tumor,but also to provide new directions for the treatment of HCC after elucidating the mechanism of tumorigenesis. |
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