title: MiR-145 negatively regulates Warburg effect by silencing KLF4 and PTBP1 in bladder cancer cells.
abstract: The Warburg effect is a well-known feature in cancer-specific metabolism. We previously reported on the role of microRNA (miR)-145 as a tumor-suppressor in human bladder cancer (BC) cells. In this study, we reveal that miR-145 decreases the Warburg effect by silencing KLF4 in BC cells. The expression levels of miR-145 were significantly lower in clinical BC samples and BC cell lines compared to those in normal tissues and HUC cells. Luciferase assay results showed that miR-145 directly bound to 3'UTR of KLF4, which was shown to be overexpressed in the clinical BC samples using Western blot analysis and immunohistochemistry. Remarkable growth inhibition and apoptosis were induced by the ectopic expression of miR-145 or by the gene silencing of KLF4 (siR-KLF4). Also, Warburg effect-related genes such as PTBP1/PKMs were regulated by the transfection of BC cells with miR-145 or siR-KLF4. These results thus indicate that the miR-145/KLF4/PTBP1/PKMs axis is one of the critical pathways that maintain the Warburg effect in BC carcinogenesis. MiR-145 perturbed the Warburg effect by suppressing the KLF4/PTBP1/PKMs pathway in BC cells, resulting in significant cell growth inhibition.
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu 501-1193, Japan.|Department of Urology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Minami
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu 501-1193, Japan.|Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Taniguchi
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu 501-1193, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Sugito
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu 501-1193, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kuranaga
authors.affiliation: Department of Urology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Inamoto
authors.affiliation: Department of Urology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takahara
authors.affiliation: Department of Urology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Takai
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu 501-1193, Japan.|Department of Urology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yoshikawa
authors.affiliation: Department of Urology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kiyama
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu 501-1193, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Akao
authors.affiliation: Department of Urology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Haruhito
authors.initials: H
authors.lastname: Azuma
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics*; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; C450006:PTBP1 protein, human; D038941:Polypyrimidine Tract-Binding Protein
keywords: KLF4; Warburg effect; bladder cancer; miR-145