MiR-652-5p elevated glycolysis level by targeting TIGAR in T-cell acute lymphoblastic leukemia

作者全名："Liu, Shan; Wang, Haobiao; Guo, Wei; Zhou, Xiaoyan; Shu, Yi; Liu, Haiyan; Yang, Li; Tang, Shi; Su, Hongyu; Liu, Ziyang; Zeng, Lamei; Zou, Lin"

作者地址："[Liu, Shan; Wang, Haobiao; Shu, Yi; Tang, Shi; Su, Hongyu; Liu, Ziyang; Zeng, Lamei; Zou, Lin] Chongqing Med Univ, Childrens Hosp, Newborn Screening Ctr, Ctr Clin Mol Lab Med, Chongqing 400014, Peoples R China; [Liu, Shan; Wang, Haobiao; Shu, Yi; Liu, Haiyan; Tang, Shi; Su, Hongyu; Liu, Ziyang; Zeng, Lamei] Natl Clin Res Ctr Child Hlth & Disorders Chongqin, Chongqing 400014, Peoples R China; [Liu, Shan; Wang, Haobiao; Shu, Yi; Liu, Haiyan; Tang, Shi; Su, Hongyu; Liu, Ziyang; Zeng, Lamei] Minist Educ, Key Lab Child Dev & Disorders, Chongqing 400014, Peoples R China; [Liu, Shan; Wang, Haobiao; Shu, Yi; Liu, Haiyan; Tang, Shi; Su, Hongyu; Liu, Ziyang; Zeng, Lamei] China Int Sci & Technol Cooperat Base Child Dev &, Chongqing 400014, Peoples R China; [Guo, Wei] Chengdu Univ, Clin Med Coll, Ctr Clin Lab, Chengdu 610081, Sichuan, Peoples R China; [Guo, Wei] Chengdu Univ, Affiliated Hosp, Chengdu 610081, Sichuan, Peoples R China; [Zhou, Xiaoyan] Qingdao Univ, Affiliated Hosp, Ctr Clin Lab, Qingdao 266101, Shandong, Peoples R China; [Liu, Haiyan] Chongqing Med Univ, Childrens Hosp, Ctr Pediat Hematol Dis, Chongqing 400014, Peoples R China; [Yang, Li] Chongqing Med Univ, Affiliated Hosp 1, Ctr Hematol Dis, Chongqing 400014, Peoples R China; [Zou, Lin] Shanghai Jiao Tong Univ, Childrens Hosp, Clin Res Unit, Shanghai 200062, Peoples R China; [Zou, Lin] Shanghai Jiao Tong Univ, Sch Med, Inst Pediat Infect Immun & Crit Care Med, Shanghai 200062, Peoples R China"

通信作者："Zou, L (通讯作者)，Chongqing Med Univ, Childrens Hosp, Newborn Screening Ctr, Ctr Clin Mol Lab Med, Chongqing 400014, Peoples R China.; Zou, L (通讯作者)，Shanghai Jiao Tong Univ, Childrens Hosp, Clin Res Unit, Shanghai 200062, Peoples R China.; Zou, L (通讯作者)，Shanghai Jiao Tong Univ, Sch Med, Inst Pediat Infect Immun & Crit Care Med, Shanghai 200062, Peoples R China."

来源：CELL DEATH & DISEASE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000755159400008

JCR分区：Q1

影响因子：9

年份：2022

卷号：13

期号：2

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："The effect of glycolysis remains largely elusive in acute T lymphoblastic leukemia (T-ALL). Increasing evidence has indicated that the dysregulation of miRNAs is involved in glycolysis, by targeting the genes coding glycolysis rate-limiting enzymes. In our previous studies, we found that overexpression of the ARRB1-derived miR-223 sponge repressed T-ALL progress and reduced the expression of miR-652-5p. However, little is known about miR-652-5p on T-ALL. Here, we showed that impaired miR-652-5p expression inhibited growth, promoted apoptosis of T-ALL cells in vitro and prolonged overall survival (OS) in vivo. Based on the GO enrichment of miR-652-5p target genes, we uncovered that impaired miR-652-5p decreased glycolysis, including reduced the lactate, pyruvate, ATP level and the total extracellular acidification rate (ECAR), elevated oxygen consumption rate (OCR) in T-ALL cell lines. Mechanically, miR-652-5p targeted the 3UTR of Tigar mRNA and inhibited its expression. Furthermore, the alteration of glycosis level was attributed to Tigar overexpression, consistent with the effect of impaired miR-652-5p. Additionally, Tigar suppressed the expression of PFKFB3, a glycolysis rate-limiting enzyme, in vivo and in vitro. Taken together, our results demonstrate that impaired miR-652-5p/Tigar axis could repress glycolysis, thus to slow growth of T-ALL cells, which support miR-652-5p as a novel potential drug target for T-ALL therapeutics."

基金机构："National Natural Science Foundation of China [81800186, 81870126, 82070167]; Science Foundation of ChongQing [cstc2021jcyj-msxmX0258]"

基金资助正文："This work was supported in part by research grants from the National Natural Science Foundation of China (81800186, 81870126, and 82070167) and Science Foundation of ChongQing (cstc2021jcyj-msxmX0258). These funders had no role in study design, data collection, and analysis, preparation of the paper, or decision to publish."