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| 1 | Activation of the Melanocortin-4 receptor signaling byα-MSH stimulates nervedependent mouse digit regeneration显示文摘Background:Expression of Mc4r in peripheral organs indicates it has broader roles in organ homeostasis and regeneration.However,the expression and function of Mc4r in the mouse limb and digit has not been fully investigated.Our previous work showed that Mc4r−/−mice fail to regenerate the digit,but whether activation of MC4R signaling could rescue digit regeneration,or stimulate proximal digit regeneration is not clear.Results:We analyzed the expression dynamics of Mc4r in the embryonic and postnatal mouse limb and digit using the Mc4r-gfp mice.We found that Mc4r-GFP is mainly expressed in the limb nerves,and in the limb muscles that are undergoing secondary myogenesis.Expression of Mc4r-GFP in the adult mouse digit is restricted to the nail matrix.We also examined the effect ofα-MSH on mouse digit regeneration.We found that administration ofα-MSH in the Mc4r+/−mice rescue the delayed regeneration of distal digit tip.α-MSH could rescue distal digit regeneration in denervated hindlimbs.In addition,α-MSH could stimulate regeneration of the proximally amputated digit,which is non-regenerative.Conclusions:Mc4r expression in the mouse limb and digit is closely related to nerve tissues,andα-MSH/MC4R signaling has a neurotrophic role in mouse digit tip regeneration. | Hanqian Xu Hailin Zhang Yanqing Fang Huiran Yang Ying Chen Chao Zhang Gufa Lin | 2021 | Cell Regeneration2021，10，1： | 1 |
| 2 | Variant rs8400 enhances ALKBH5 expression through disrupting miR-186 binding and promotes neuroblastoma progression显示文摘Objective:AlkB homolog 5(ALKBH5)has been proven to be closely related to tumors.However,the role and molecular mechanism of ALKBH5 in neuroblastomas have rarely been reported.Methods:The potential functional single-nucleotide polymorphisms(SNPs)in ALKBH5 were identified by National Center for Biotechnology Information(NCBI)dbSNP screening and SNPinfo software.TaqMan probes were used for genotyping.A multiple logistic regression model was used to evaluate the effects of different SNP loci on the risk of neuroblastoma.The expression of ALKBH5 in neuroblastoma was evaluated by Western blotting and immunohistochemistry(IHC).Cell counting kit-8(CCK-8),plate colony formation and 5-ethynyl-2'-deoxyuridine(EdU)incorporation assays were used to evaluate cell proliferation.Wound healing and Transwell assays were used to compare cell migration and invasion.Thermodynamic modelling was performed to predict the ability of miRNAs to bind to ALKBH5 with the rs8400 G/A polymorphism.RNA sequencing,N6-methyladenosine(mA)sequencing,mA methylated RNA immunoprecipitation(MeRIP)and a luciferase assay were used to identify the targeting effect of ALKBH5 on SPP1.Results:ALKBH5 was highly expressed in neuroblastoma.Knocking down ALKBH5 inhibited the proliferation,migration and invasion of cancer cells.miR-186-3p negatively regulates the expression of ALKBH5,and this ability is affected by the rs8400 polymorphism.When the G nucleotide was mutated to A,the ability of miR-186-3p to bind to the 3'-UTR of ALKBH5 decreased,resulting in upregulation of ALKBH5.SPPI is the downstream target gene of the ALKBH5 oncogene.Knocking down SPP1 partially restored the inhibitory effect of ALKBH5 downregulation on neuroblastoma.Downregulation of ALKBH5 can improve the therapeutic efficacy of carboplatin and etoposide in neuroblastoma.Conclusions:We first found that the rs8400 G>A polymorphism in the m6A demethylase-encoding gene ALKBH5 increases neuroblastoma susceptibility and determines the related mechanisms.The aberrant regulation of ALKBH5 by miR-186-3p caused by this genetic variation in ALKBH5 promotes the occurrence and development of neuroblastoma through the ALKBH5-SPP1 axis. | Qian Guan Huiran Lin Wenfeng Hua Lei Lin Jiabin Liu Linqing Deng Jiao Zhang Jiwen Cheng Zhonghua Yang Yong Li Jun Bian Haixia Zhou Suhong Li Li Li Lei Miao Huimin Xia Jing He Zhenjian Zhuo | 2023 | Chinese Journal of Cancer Research2023，35，2： | 0 |
| 3 | PTBP2-Mediated Alternative Splicing of IRF9 Controls Tumor-Associated Monocyte/Macrophage Chemotaxis and Repolarization in Neuroblastoma Progression显示文摘The recurrence and metastasis of children with mediastinal neuroblastoma(NB)are also occurred after surgery,chemotherapy,or radiotherapy.Strategies targeting the tumor microenvironment have been reported to improve survival;however,thorough investigations of monocytes and tumor-associated macrophages(Mϕs)with specialized functions in NB are still lacking.Our data first demonstrated polypyrimidine tract binding protein 2(PTBP2)as a possible identifier in patients with mediastinal NB screened by proteomic profiling and that PTBP2 predicted good outcomes.Functional studies revealed that PTBP2 in NB cells induced the chemotactic activity and repolarization of tumor-associated monocytes and Mϕs,which,in turn,inhibited NB growth and dissemination.Mechanistically,PTBP2 prevents interferon regulatory factor 9 alternative splicing and upregulates signal transducers and activators of transcription 1 to stimulate C-C motif chemokine ligand 5(CCL5)and interferon-stimulated gene factor-dependent type I interferon secretion,to induce monocyte/Mϕs chemotaxis,and to sustain monocytes in a proinflammatory phenotype.Our study defined a critical event of PTBP2-induced monocytes/Mϕs in NB progression and revealed that RNA splicing occurred by PTBP2 benefits immune compartmentalization between NB cells and monocytes.This work revealed the pathological and biological role of PTBP2 in NB development and indicates that PTBP2-induced RNA splicing benefits immune compartmentalization and predicted a favorable prognosis in mediastinal NB. | Jue Tang Jing He Huiqin Guo Huiran Lin Meng Li Tianyou Yang Hai-Yun Wang Di Li Jiabin Liu Le Li Huimin Xia Zhenjian Zhuo Lei Miao | 2023 | Research2023，，3： | 0 |
| 4 | Associations between LMO1 gene polymorphisms and central nervous system tumor susceptibility显示文摘Importance:LIM domain only 1(LMO1)gene polymorphisms were previously found to be implicated in the risk of several cancers.No available studies were performed regarding the predisposing effect of LMO1 gene single nucleotide polymorphisms(SNPs)on central nervous system(CNS)tumor risk.Objective:We aimed to determine whether the LMO1 gene SNPs were associated with the risk of CNS tumor by applying a case-control study with 191 cases and 248 controls in China.Methods:The contributions of LMO1 gene SNPs to the risk of CNS tumor was evaluated by multinomial logistic regression.Results:Based on the calculations of odds ratio(OR)and 95%confidence interval(CI),we failed to detect a significant relationship between each LMO1 gene SNP(rs110419 A>G,rs4758051 G>A,rs10840002 A>G,rs204938 A>G,and rs2168101 G>T)and CNS tumor risk,respectively.A negative association was also found in the combined effects on these five SNPs and CNS tumor risk.The stratification analysis further demonstrated the individuals with rs204938 AG/GG genotype confer to increased risk of CNS tumor compared with those with an AA genotype in males(OR:1.74,95%CI:1.01-2.98,P=0.046).Interpretation:We concluded that LMO1 gene SNPs may not strong enough to influence the risk of CNS tumor in Chinese children.More studies are required to verify this association. | Huiran Lin Huitong Chen Ao Lin Xiaoping Liu Xiaokai Huang Jingying Zhou Li Yuan Zhenjian Zhuo | 2021 | Pediatric Investigation2021，5，4： | 0 |
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