LncRNA <i>AC142119</i>.<i>1</i> facilitates the progression of neuroblastoma by epigenetically initiating the transcription of <i>MYCN</i>

作者全名："Yang, Rui; Liu, Nanjing; Li, Ting; Liu, Fangjie; Zhang, Jun; Zhao, Hui; Zou, Lin; He, Xiaoyan"

作者地址："[Yang, Rui; Liu, Nanjing; Liu, Fangjie; Zou, Lin; He, Xiaoyan] Chongqing Med Univ, Childrens Hosp,Natl Clin Res Ctr Child Hlth & Dis, Key Lab Child Dev & Disorders,Chongqing Key Lab P, China Int Sci & Technol Cooperat Base Child Dev &, Chongqing 400014, Peoples R China; [Liu, Nanjing] Chongqing Univ, Canc Hosp, Chongqing Key Lab Translat Res Canc Metastasis &, Chongqing 400030, Peoples R China; [Li, Ting] Chongqing Med Univ, Key Lab Lab Med Diagnost, Minist Educ, Chongqing 400016, Peoples R China; [Zhang, Jun] Chongqing Med Univ, Childrens Hosp, Dept Oncol Surg, Chongqing 400014, Peoples R China; [Zhao, Hui] Chinese Univ Hong Kong, Sch Biomed Sci, Fac Med, Hong Kong 999077, Peoples R China; [Zou, Lin] Shanghai Jiao Tong Univ, Sch Med, Inst Pediat Infect Immun & Crit Care Med, Childrens Hosp,Clin Res Unit, Shanghai 200062, Peoples R China"

通信作者："Zou, L; He, XY (通讯作者)，Chongqing Med Univ, Childrens Hosp,Natl Clin Res Ctr Child Hlth & Dis, Key Lab Child Dev & Disorders,Chongqing Key Lab P, China Int Sci & Technol Cooperat Base Child Dev &, Chongqing 400014, Peoples R China.; Zou, L (通讯作者)，Shanghai Jiao Tong Univ, Sch Med, Inst Pediat Infect Immun & Crit Care Med, Childrens Hosp,Clin Res Unit, Shanghai 200062, Peoples R China."

来源：JOURNAL OF TRANSLATIONAL MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001124793200001

JCR分区：Q1

影响因子：6.1

年份：2023

卷号：21

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Neuroblastoma; lncRNA AC142119.1; MYCN; WDR5

摘要："Background Oncogene MYCN is closely related with malignant progression and poor prognosis of neuroblastoma (NB). Recently, long non-coding RNAs (lncRNAs) have been recognized as crucial regulators in various cancers. However, whether lncRNAs contribute to the overexpression of MYCN in NB is unclear. Methods Microarray analysis were applied to analyze the differentially expressed lncRNAs between MYCN-amplified and MYCN-non-amplified NB cell lines. Bioinformatic analyses were utilized to identify lncRNAs nearby MYCN locus. qRT-PCR was used to detect the expression level of lncRNA AC142119.1 in NB cell lines and tissues. Gain- and loss-of-function assays were conducted to investigate the biological effect of AC142119.1 in NB. Fluorescence in situ hybridization, RNA pull-down, RNA immunoprecipitation, mass spectrometry, RNA electrophoretic mobility shift, chromatin immunoprecipitation and chromatin isolation by RNA purification assays were performed to validate the interaction between AC142119.1 and WDR5 protein as well as MYCN promoter. Results AC142119.1 was significantly elevated in NB tissues with MYCN amplification, advanced INSS stage and high risk, and associated with poor survival of NB patients. Moreover, enforced expression of AC142119.1 reinforced the proliferation of NB cells in vitro and in vivo. Additionally, AC142119.1 specifically recruited WDR5 protein to interact with MYCN promoter, further initiating the transcription of MYCN and accelerating NB progression. Conclusions We identified a novel lncRNA AC142119.1, which promoted the progression of NB through epigenetically initiating the transcription of MYCN via interacting with both WDR5 protein and the promoter of MYCN, indicating that AC142119.1 might be a potential diagnostic biomarker and therapeutic target for NB."

基金机构："Natural Science Foundation of China [82070167, 82270160]; Chongqing Bureau of Science and Technology [2021MSXM167]; Chongqing Municipal Health Commission [2021MSXM167]; General Basic Research Project from the Ministry of Education Key Laboratory of Child Development and Disorders [GBRP-202103]; Chongqing Graduate Scientific Research Innovation Project [CYB19154]"

基金资助正文："This study was partially supported by Natural Science Foundation of China (82070167, 82270160), the Chongqing Bureau of Science and Technology and Chongqing Municipal Health Commission joint research project (2021MSXM167), the General Basic Research Project from the Ministry of Education Key Laboratory of Child Development and Disorders (GBRP-202103) and Chongqing Graduate Scientific Research Innovation Project (CYB19154)."