光催化下二芳基碘鎓盐参与的自由基芳基化反应研究进展

二芳基高价碘盐在有机合成中被广泛应用.总结了二芳基高价碘试剂在可见光诱导的自由基芳基化反应中的研究进展.根据反应类型,分为碳碳键的形成、碳硫键的形成和碳膦键的形成三部分进行综述.

GPR162 activates STING dependent DNA damage pathway as a novel tumor suppressor and radiation sensitizer

In the treatment of most malignancies,radiotherapy plays a significant role.However,the resistance of cancer cells to ionizing radiation(IR)is the main reason for the failure of radiotherapy,which causes tumor recurrence and metastasis.In this study,we confirmed that GPR162,an orphan receptor in the G-protein-coupled receptor family,acted as a novel radiotherapy sensitizer by interacting with the stimulator of interferon genes(STING),which targeted DNA damage responses,activated IRF3,accelerated the activation of type I interferon system,promoted the expression of chemokines including CXCL10 and CXCL4,and inhibited the occurrence and development of tumors.Interestingly,the activation of STING by overexpression of GPR162 was independent of the classical pathway of cGAS.STING inhibitors could resist the antitumor effect of overexpression of GPR162 in IR-induced mouse models.In addition,most solid tumors showed low expression of GPR162.And the higher expression of GPR162 indicated a better prognosis in patients with lung adenocarcinoma,liver cancer,breast cancer,etc.In summary,these results suggested that GPR162 may serve as a potential sensitizer of radiotherapy by promoting radiotherapy-induced STING-IFN production and increasing the expression of chemokines including CXCL10 and CXCL4 in DNA damage response,providing an alternative strategy for improving cancer radiotherapy.

The deubiquitylase UCHL3 maintains cancer stem-like properties by stabilizing the aryl hydrocarbon receptor

Cancer stem cells(CSCs)exhibit highly aggressive and metastatic features and resistance to chemotherapy and radiotherapy.Aryl hydrocarbon receptor(AhR)expression varies among non-small cell lung cancers(NSCLCs),and the mechanisms that support abnormal AhR expression in CSCs remain elusive.Here,we identified ubiquitin carboxyl terminal hydrolase L3(UCHL3),a DUB enzyme in the UCH protease family,as a bona fide deubiquitylase of the AhR in NSCLC.UCHL3 was shown to interact with,deubiquitylate,and stabilize AhR in a manner dependent on its deubiquitylation activity.Moreover,we showed that UCHL3 promotes the stem-like characteristics and potent tumorigenic capacity of NSCLC cells.UCHL3 increased AhR stability and the binding of AhR to the promoter regions of the“stemness”genes ATP-binding cassette subfamily G member 2(ABCG2),KLF4,and c-Myc.Depletion of UCHL3 markedly downregulated the“stemness”genes ABCG2,KLF4,and c-Myc,leading to the loss of selfrenewal and tumorigenesis in NSCLCs.Furthermore,the UCHL3 inhibitor TCID induced AhR degradation and exhibited significantly attenuated efficacy in NSCLC cells with stem cell-like properties.Additionally,UCHL3 was shown to indicate poor prognosis in patients with lung adenocarcinoma.In general,our results reveal that the UCHL3 deubiquitylase is pivotal for AhR protein stability and a potential target for NSCLC-targeted therapy.

Author Correction:GPR162 activates STING dependent DNA damage pathway as a novel tumor suppressor and radiation sensitizer

Since the publication of this article,we noticed a minor mistake in the article that needs to be corrected.We have checked the original data;the correct data are provided in this Corrigendum as follows.The key findings of the article are not affected by these corrections.

IL4I1-driven AHR signature: a new avenue for cancer therapy

Aryl hydrocarbon receptor(AHR)was considered to be an important pan-tumor therapeutic target,but small molecule inhibitors targeting AHR target gene ID01 have failed in clinical trials.The recent paper published in Cell by Opitz et al.explained the failure of previous clinical trials and identified new therapeutic targets(Fig.1).

The cross-talk between methylation and phosphorylation in lymphoid-specific helicase drives cancer stem-like properties

Posttranslational modifications(PTMs)of proteins,including chromatin modifiers,play crucial roles in the dynamic alteration of various protein properties and functions including stem-cell properties.However,the roles of Lymphoid-specific helicase(LSH),a DNA methylation modifier,in modulating stem-like properties in cancer are still not clearly clarified.Therefore,exploring PTMs modulation of LSH activity will be of great significance to further understand the function and activity of LSH.Here,we demonstrate that LSH is capable to undergo PTMs,including methylation and phosphorylation.The arginine methyltransferase PRMT5 can methylate LSH at R309 residue,meanwhile,LSH could as well be phosphorylated by MAPK1 kinase at S503 residue.We further show that the accumulation of phosphorylation of LSH at S503 site exhibits downregulation of LSH methylation at R309 residue,which eventually promoting stem-like properties in lung cancer.Whereas,phosphorylation-deficient LSH S503A mutant promotes the accumulation of LSH methylation at R309 residue and attenuates stem-like properties,indicating the critical roles of LSH PTMs in modulating stem-like properties.Thus,our study highlights the importance of the crosstalk between LSH PTMs in determining its activity and function in lung cancer stem-cell maintenance.