miR-373-3p promotes aerobic glycolysis in colon cancer cells by targeting MFN2  

作　　者：Yu Wang Jie Lun Yuying Zhang Mengchao Yu Xingqian Liu Jing Guo Hongwei Zhang Wensheng Qiu Jing Fang 

机构地区：[1]Department of Oncology,the Affiliated Hospital of Qingdao University,Qingdao University,Qingdao Cancer Institute,Qingdao 266071,China [2]School of Basic Medicine,Qingdao University,Qingdao 266071,China [3]School of Pharmacy,Qingdao University,Qingdao 266071,China [4]School of Public Health,Qingdao University,Qingdao 266071,China [5]Central Laboratory,Qingdao Municipal Hospital,Qingdao 266071,China [6]Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University,Jinan 250014,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第10期1498-1508,共11页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from Ministry of Science and Technology of China(No.2020YFA0803301);the National Natural Science Foundation of China(No.82073061);the Natural Science Foundation of Shandong Province(No.ZR2020MH206).

摘　　要：MicroRNAs(miRNAs)are implicated in the development of cancers and may serve as potential targets for therapy.However,the functions and underlying mechanisms of miRNAs in cancers are not well understood.This work aims to study the role of miR-373-3p in colon cancer cells.We find that the expression of miR-373-3p mimics promotes and the miR-373-3p inhibitor suppresses aerobic glycolysis and proliferation of colon cancer cells.Mechanistically,miR-373-3p inhibits the expression of MFN2,a gene that is known to suppress glycolysis,which leads to the activation of glycolysis and eventually the proliferation of cells.In a nude mouse tumor model,the expression of miR-373-3p in colon cancer cells promotes tumor growth by enhancing lactate formation,which is inhibited by the co-expression of MFN2 in the cells.Administration of the miR-373-3p antagomir blunts in vivo tumor growth by decreasing lactate production.In addition,in human colon cancers,the expression levels of miR-373-3p are increased,while those of MFN2 mRNA are decreased,and the increase of miR-373-3p is associated with the decrease of MFN2 mRNA.Our results reveal a previously unknown function and underlying mechanism of miR-373-3p in the regulation of glycolysis and proliferation in cancer cells and underscore the potential of targeting miR-373-3p for colon cancer treatment.

关 键 词：miRNA colon cancer GLYCOLYSIS cell proliferation miR-373-3p MFN2 

分 类 号：R735.35[医药卫生—肿瘤]