The Citron homology domain of MAP4Ks improves outcomes of traumatic brain injury

The mitogen-activated protein kinase kinase kinase kinases(MAP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults.Whether targeting this pathway is beneficial to brain injury remains unclear.In this study,we showed that adeno-associated virus-delivery of the Citron homology domain of MAP4Ks effectively reduces traumatic brain injury-induced reactive gliosis,tauopathy,lesion size,and behavioral deficits.Pharmacological inhibition of MAP4Ks replicated the ameliorative effects observed with expression of the Citron homology domain.Mechanistically,the Citron homology domain acted as a dominant-negative mutant,impeding MAP4K-mediated phosphorylation of the dishevelled proteins and thereby controlling the Wnt/β-catenin pathway.These findings implicate a therapeutic potential of targeting MAP4Ks to alleviate the detrimental effects of traumatic brain injury.

miR-181b promotes the oncogenesis of renal cell carcinoma by targeting TIMP3

Renal cell carcinoma(RCC)has a poor prognosis due to limited diagnosis and treatment.Thus,it is necessary to find novel prognostic biomarkers and therapeutic targets.The aberrant expression of microRNAs plays an important role in RCC oncogenesis.Tissue inhibitors of metalloproteinase 3(TIMP3)acts as a downstream target of miR-181b.The aim of this study was to understand the role and molecular mechanism of miR-181b in RCC oncogenesis.The results showed that miR-181b expression was significantly higher in RCC tumour tissues,especially in those with significant invasion or metastasis.miR-181b overexpression promoted proliferation and migration of the RCC cell line 786-O,while miR-181b knockdown had the opposite effect.In addition,miR-181b was inversely correlated with TIMP3 expression in RCC tumour tissues.miR-181b overexpression reduced TIMP3 expression in RCC cell line 786-O or OS-RC-2,while miR-181b knockdown had the inverse effect.Mechanistically,a luciferase reporter assay confirmed the binding sites of miR-181b on the 3’-UTR of TIMP3,confirming the targeting effect of miR-181b on TIMP3.Overall,miR-181b promotes the development and progression of RCC by targeting TIMP3 expression,indicating the potential use of miR-181b in the diagnosis and treatment of RCC.