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-nu...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.展开更多
Azadirachta indica A. Juss is a tropical evergreen plant, belonging to the Meliaceae family. The plant is used as folk medicines for the treatment of fever, neuromuscular pains, skin infections, diabetes and heart dis...Azadirachta indica A. Juss is a tropical evergreen plant, belonging to the Meliaceae family. The plant is used as folk medicines for the treatment of fever, neuromuscular pains, skin infections, diabetes and heart disease. Previous researches show that the plant possesses several types of chemical constituents and diverse biological activities. The paper concludes chemical constituents, biological activities and pesticide products of A. indica.展开更多
In the published article by Zhou et al.,1 two errors were found in Figure 2c and Figure 3a.In Figure 2c,two labels of abscissa“Norm”and“ATZ”were reversed.In Figure 3a,the scale values of abscissa were not consiste...In the published article by Zhou et al.,1 two errors were found in Figure 2c and Figure 3a.In Figure 2c,two labels of abscissa“Norm”and“ATZ”were reversed.In Figure 3a,the scale values of abscissa were not consistent with those in Figure 3b,Figure 4a,and Figure 4b.This error occurred due to mislabeling of the computer file folders,in which images collected from similar categories of experiments were stored.The authors replotted Figure 3c according to original data.The correct Figure 2 and 3 are as follows.展开更多
To the Editor:Glioma is a highly invasive and lethal heterogeneous disease caused by glial or precursor cell mutation.It accounts for about 50%of tumors in children and 80%of malignant tumors.[1]The nucleotide excisio...To the Editor:Glioma is a highly invasive and lethal heterogeneous disease caused by glial or precursor cell mutation.It accounts for about 50%of tumors in children and 80%of malignant tumors.[1]The nucleotide excision repair(NER)pathway is a process that involves the sequential assembly of many proteins,including excision repair cross complementation group 1(ERCC1)and xeroderma pigmentosum complementation group F(XPF,also known as ERCC4).展开更多
Glioma is an aggressive malignant primary tumor in the central nervous system[1,2].Although the pathogenesis of glioma is unclear,the only identified environmental risk fac-tor is ionizing radiation[3].However,other f...Glioma is an aggressive malignant primary tumor in the central nervous system[1,2].Although the pathogenesis of glioma is unclear,the only identified environmental risk fac-tor is ionizing radiation[3].However,other factors also may alter the glioma risk,among which gene polymorphisms may play prominent role in glioma susceptibility.Base excision repair(BER)is a DNA repair mechanism that maintains genome integrity and guarantees DNA base modification properly.Many signifcant and common proteins involved in the BER pathway are associated with cancer.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.82002635,82002636and 82173593)GuangzhouScienceand TechnologyProject(No.202102021227 and202102020421)+1 种基金the Science Technology and Innovation Commission of Shenzhen(No.JCYJ20220531093213030)Guangzhou Municipal Basic Research Program Joint Funding of City and Hospitals(No.202201020622).
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.
基金the China High-Tech Development 863 Program,Guangdong Province Sci & Tech Bureau(No.2006B12401006)Guangzhou Sci & Tech Bureau(No.2005U13D2031,2007Z2-D2031)financial support of this work National University of Singapore for financial support.
文摘Novel Cu-Ni/C has been prepared and utilized as an efficient catalyst system in direct synthesis of DMC from CH_3OH and CO_2.
文摘Azadirachta indica A. Juss is a tropical evergreen plant, belonging to the Meliaceae family. The plant is used as folk medicines for the treatment of fever, neuromuscular pains, skin infections, diabetes and heart disease. Previous researches show that the plant possesses several types of chemical constituents and diverse biological activities. The paper concludes chemical constituents, biological activities and pesticide products of A. indica.
文摘In the published article by Zhou et al.,1 two errors were found in Figure 2c and Figure 3a.In Figure 2c,two labels of abscissa“Norm”and“ATZ”were reversed.In Figure 3a,the scale values of abscissa were not consistent with those in Figure 3b,Figure 4a,and Figure 4b.This error occurred due to mislabeling of the computer file folders,in which images collected from similar categories of experiments were stored.The authors replotted Figure 3c according to original data.The correct Figure 2 and 3 are as follows.
基金supported by grants from the National Natural Science Foundation of China(No.81802346)the China Postdoctoral Science Foundation(Nos.2020T130132,2020M682668)
文摘To the Editor:Glioma is a highly invasive and lethal heterogeneous disease caused by glial or precursor cell mutation.It accounts for about 50%of tumors in children and 80%of malignant tumors.[1]The nucleotide excision repair(NER)pathway is a process that involves the sequential assembly of many proteins,including excision repair cross complementation group 1(ERCC1)and xeroderma pigmentosum complementation group F(XPF,also known as ERCC4).
基金The authors would like to thank the Key Research Fund Program of Xihua University(No.Z0910109)for financial support of this researchZ.Guan.thanks National University of Singapore for financial support
基金The authors would like to thank Prof. Chunyan Wang, for her contributions to the samples collection, as well as thank Cheng Yang for his contributions to the figures revision. This study was supported by the Guangdong Provincial Natural Science Foundation of China （No. 2014A030313291, No. 2015A030310027 and No. 2016A030310393）, the Guangdong Provincial Science and Technology Program （No. 2014A020212204）, and the Science and Technology Innovation Project of Southern Medical University （QD2014N005）.
基金supported by grants from the National Natural Science Foundation of China(81802346)the Discipline Promotion Project of the First Affiliated Hospital of Air Force Medical University(XJZT18MJ49).
文摘Glioma is an aggressive malignant primary tumor in the central nervous system[1,2].Although the pathogenesis of glioma is unclear,the only identified environmental risk fac-tor is ionizing radiation[3].However,other factors also may alter the glioma risk,among which gene polymorphisms may play prominent role in glioma susceptibility.Base excision repair(BER)is a DNA repair mechanism that maintains genome integrity and guarantees DNA base modification properly.Many signifcant and common proteins involved in the BER pathway are associated with cancer.
