title: Negative regulation of Bmi-1 by AMPK and implication in cancer progression.
abstract: Bmi-1 is a transcriptional regulator that promotes tumor cell self-renewal and epithelial to mesenchymal transition and its upregulation is associated with tumor progression, AMPK is an intracellular fuel-sensing enzyme and plays important roles in tumor cell growth and progression. Thus, the present study aims to examine the regulation of Bmi-1 by AMPK. First, our data revealed that, as compared to adjacent normal tissue, Bmi-1 was highly expressed in gastric cancer, whereas phosphorylation of AMPK (p-AMPK) was reduced. Similar findings were observed in lung adenocarcinomas and appeared that the expression of Bmi-1 was correlated with pathological grades of the cancer, where opposite changes were found in p-AMPK. Second, Metformin, a pharmacological AMPK activator and anti-diabetic drug, or ectopic expression of LKB1, diminished expression of Bmi-1 in cancer cells, an event that was reversed by silencing LKB1. Third, knockdown of LITAF, previously identified as a downstream target of AMPK, upregulated Bmi-1, associated with increased cell viability, colony formation, and migration of cancer cells in vitro. Fourth, metformin increased the abundance of miR-15a, miR-128, miR-192, and miR-194, which was prevented by knockdown of LITAF. Accordingly, transfection of these individual miRNAs downregulated Bmi-1. Altogether, our data for the first time suggest a regulatory axis in cancer cells: AMPK upregulates LITAF, which in turn increases miRNAs, leading to attenuation of Bmi-1 expression.
authors.affiliation: Research Institute of Digestive Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Deqiang
authors.initials: D
authors.lastname: Huang
authors.affiliation: Graduate Program, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, P.R. China.|Institute of Basic Medical Sciences, Nanchang University, Nanchang, Jiangxi, P.R. China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: He
authors.affiliation: Graduate Program, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, P.R. China.|Institute of Basic Medical Sciences, Nanchang University, Nanchang, Jiangxi, P.R. China.
authors.forename: Junrong
authors.initials: J
authors.lastname: Zou
authors.affiliation: Graduate Program, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, P.R. China.|Institute of Basic Medical Sciences, Nanchang University, Nanchang, Jiangxi, P.R. China.
authors.forename: Pei
authors.initials: P
authors.lastname: Guo
authors.affiliation: Graduate Program, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, P.R. China.|Institute of Basic Medical Sciences, Nanchang University, Nanchang, Jiangxi, P.R. China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Research Institute of Digestive Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Nonghua
authors.initials: N
authors.lastname: Lv
authors.affiliation: Departments of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Alekseyev
authors.affiliation: Research Institute of Digestive Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Luo
authors.affiliation: Institute of Basic Medical Sciences, Nanchang University, Nanchang, Jiangxi, P.R. China.|Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Luo
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000230:Adenocarcinoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D018450:Disease Progression; D057809:HEK293 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D063150:Polycomb Repressive Complex 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology
chemical_list: C069077:BMI1 protein, human; D063150:Polycomb Repressive Complex 1; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Bmi-1; LITAF; cancer progression; miRNA