Variant rs8400 enhances ALKBH5 expression through disrupting miR-186 binding and promotes neuroblastoma progression

doi:10.21147/j.issn.1000-9604.2023.02.05

科研成果详情

题名	Variant rs8400 enhances ALKBH5 expression through disrupting miR-186 binding and promotes neuroblastoma progression
作者	Guan, Qian 1,2; Lin, Huiran 3; Hua, Wenfeng 4; Lin, Lei 1; Liu, Jiabin 1; Deng, Linqing 1; Zhang, Jiao 5; Cheng, Jiwen 6; Yang, Zhonghua 7; Li, Yong 8; Bian, Jun 9; Zhou, Haixia10,11; Li, Suhong 12; Li, Li 13; Miao, Lei 1; Xia, Huimin 1; He, Jing 1,2; Zhuo, Zhenjian 1,2,14
发表日期	2023-04
发表期刊	CHINESE JOURNAL OF CANCER RESEARCH 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Neuroblastoma risk ALKBH5 polymorphism progression
其他关键词	HIGH-RISK NEUROBLASTOMA ; RNA DEMETHYLASE ALKBH5 ; GENETIC PREDISPOSITION ; CANCER ; N-6-METHYLADENOSINE ; SUSCEPTIBILITY ; PROLIFERATION ; CHEMOTHERAPY ; MUTATIONS ; SURVIVAL
摘要	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 (m6A) sequencing, m6A 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. SPP1 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.
资助项目	National Natural Science Foundation of China [82002635, 82002636, 82173593]; Guangzhou Science and Technology Project [202102021227, 2021 02020421]; Science Technology and Innovation Commission of Shenzhen [JCYJ20220531093213030]; Guangzhou Municipal Basic Research Program Joint Funding of City and Hospitals [202201020622]
出版者	CHINESE JOURNAL CANCER RESEARCH CO
ISSN	1000-9604
EISSN	1993-0631
卷号	35 期号:2 页码:140-+
DOI	10.21147/j.issn.1000-9604.2023.02.05
页数	28
WOS类目	Oncology
WOS研究方向	Oncology
WOS记录号	WOS:000993122000005
收录类别	SCIE ; PUBMED
URL	查看原文
PubMed ID	37180836
通讯作者地址	[He, Jing]Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Guangdong Prov Clin Res Ctr Child Hlth, Dept Pediat Surg,Guangzhou Inst Pediat,Guangdong, Guangzhou 510623, Peoples R China. ; [Zhuo, Zhenjian]Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Guangzhou Inst Pediat, Dept Pediat Surg, Guangzhou 510623, Peoples R China.
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/180012
专题	附属第二医院_血液内科第二临床医学院，附属第二医院、育英儿童医院
通讯作者	He, Jing; Zhuo, Zhenjian
作者单位	1.South China Univ Technol, Sch Med, Guangzhou 510006, Peoples R China; 2.Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Guangdong Prov Clin Res Ctr Child Hlth, Dept Pediat Surg,Guangzhou Inst Pediat,Guangdong, Guangzhou 510623, Peoples R China; 3.Macau Univ Sci & Technol, Fac Med, Taipa 999078, Macau, Peoples R China; 4.Guangdong Second Prov Gen Hosp, Res Inst Maternal & Child Hlth, Guangzhou 510317, Peoples R China; 5.Zhengzhou Univ, Affiliated Hosp 1, Dept Pediat Surg, Zhengzhou 450052, Peoples R China; 6.Xi An Jiao Tong Univ, Affiliated Hosp 2, Dept Pediat Surg, Xian 710004, Peoples R China; 7.China Med Univ, Shengjing Hosp, Dept Pediat Surg, Shenyang 110004, Peoples R China; 8.Hunan Childrens Hosp, Dept Pediat Surg, Changsha 410004, Peoples R China; 9.Xi An Jiao Tong Univ, Xian Childrens Hosp, Affiliated Childrens Hosp, Dept Gen Surg, Xian 710003, Peoples R China; 10.Wenzhou Med Univ, Affiliated Hosp 2, Dept Hematol, Wenzhou 325027, Peoples R China; 11.Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou 325027, Peoples R China; 12.Children Hosp & Women Hlth Ctr Shanxi, Dept Pathol, Taiyuan 030013, Peoples R China; 13.Kunming Childrens Hosp, Kunming Key Lab Children Infect & Immun, Yunnan Key Lab Childrens Major Dis Res, Yunnan Inst Pediat Res,Yunnan Med Ctr Pediat Dis, Kunming 650228, Peoples R China; 14.Peking Univ, Shenzhen Grad Sch, Lab Anim Ctr, Sch Chem Biol & Biotechnol, Shenzhen 518055, Peoples R China
推荐引用方式 GB/T 7714	Guan, Qian,Lin, Huiran,Hua, Wenfeng,et al. Variant rs8400 enhances ALKBH5 expression through disrupting miR-186 binding and promotes neuroblastoma progression[J]. CHINESE JOURNAL OF CANCER RESEARCH,2023,35(2):140-+.
APA	Guan, Qian., Lin, Huiran., Hua, Wenfeng., Lin, Lei., Liu, Jiabin., ... & Zhuo, Zhenjian. (2023). Variant rs8400 enhances ALKBH5 expression through disrupting miR-186 binding and promotes neuroblastoma progression. CHINESE JOURNAL OF CANCER RESEARCH, 35(2), 140-+.
MLA	Guan, Qian,et al."Variant rs8400 enhances ALKBH5 expression through disrupting miR-186 binding and promotes neuroblastoma progression".CHINESE JOURNAL OF CANCER RESEARCH 35.2(2023):140-+.