Long noncoding RNAs(IncRNAs)are involved in a variety of cancers,but the role of LncRNA DUBR in lung adenocarcinoma(LUAD),the most prevalent form of lung cancer,remains unclear.In this study we investigated the expression of DUBR in LUAD to ascertain its association with the clinical pathology and prognosis of LUAD.Analysis of mRNA expression in The Cancer Genome Atlas(TCGA)LUAD database and in-house LUAD cohort(n=94)showed that DUBR was significantly downregulated in LUAD,and was associated with poor prognosis.In LUAD cell lines(H1975,A549),overexpression of DUBR significantly suppressed the migration and invasion of the LUAD cells.We demonstrated that c-Myc could bind to the promoter of DUBR,and transcriptionally suppressed its expression.Knockdown of c-Myc almost completely blocked the invasion and migration of LUAD cells,whereas knockdown of DUBR partially rescued c-MMyc-knockdown suppressed cell migration and invasion.Furthermore,DUBR overexpression significantly increased the expression of a downstream protein of DUBR,zinc finger,and BTB domain containing 11(ZBTB11),in H1975 and A549 cells;knockdown of ZBTB11 partially rescued the DUBR-overexpression suppressed cell migration and invasion;knockdown of c-Myc significantly upregulated the expression of ZBTB11 in LUAD cells.Finally,we revealed that DUBR/ZBTB11 axis suppressed oxidative phosphorylation in LUAD cells.In short,we demonstrate that c-Myc/DUBR/ZBTB11 axis suppresses migration and invasion of LUAD by attenuating cell oxidative phosphorylation,which provides new insights into the regulatory mechanism of DUBR.

Wei Nie;Min-juan Hu;Qin Zhang;Jun Lu;Fang-fei Qian;Le-le Zhang;Fang Hu;Chang-hui Li;Shu-hui Cao;Jing-wen Li;Yue Wang;Xue-yan Zhang;Mi-die Xu;Bao-hui Han

Department of Pulmonary Medicine,Shanghai Chest Hospital,Shanghai Jiao Tong University,Shanghai 200030,China;Department of Radiation Oncology,Shanghai Chest Hospital,Shanghai Jiao Tong University,Shanghai 200030,China;Department of Pathology,Fudan University Shanghai Cancer Center,Shanghai 200032,China;Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,China;Institute of Pathology,Fudan University,Shanghai 200032,China

中国药理学报（英文版）

[1]Wei Nie;Min-juan Hu;Qin Zhang;Jun Lu;Fang-fei Qian;Le-le Zhang;Fang Hu;Chang-hui Li;Shu-hui Cao;Jing-wen Li;Yue Wang;Xue-yan Zhang;Mi-die Xu;Bao-hui Han-.DUBR suppresses migration and invasion of human lung adenocarcinoma cells via ZBTB11-mediated inhibition of oxidative phosphorylation)[J].中国药理学报（英文版）,2022(01):157-166

DUBR,ZBTB11,MMyc

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