title: MicroRNA-124 inhibits cancer cell growth through PTB1/PKM1/PKM2 feedback cascade in colorectal cancer.
abstract: Altered levels and functions of microRNAs (miRs) have been associated with carcinogenesis. In this study, we investigated the role of miR-124 in colorectal adenoma (CRA) and cancer (CRC). The expression levels of miR-124 were decreased in CRA (81.8%) and CRC (57.6%) in 55 clinical samples. The ectopic expression of miR-124 induced apoptosis and autophagy in colon cancer cells. Also, miR-124 targeted polypyrimidine tract-binding protein 1 (PTB1), which is a splicer of pyruvate kinase muscles 1 and 2 (PKM1 and PKM2) and induced the switching of PKM isoform expression from PKM2 to PKM1. Also, siR-PTB1 induced drastic apoptosis in colon cancer cells. Furthermore, we found that the ectopic expression of miR-124 enhanced oxidative stress and the miR-124/PTB1/PKM1/PKM2 axis constituted a feedback cascade. Finally, we showed that intratumor injection of miR-124 and siR-PTB1 induced a tumor-suppressive effect in xenografted mice. The axis was established by both in vitro and in vivo experiments to function in human colorectal cancer cells. These findings suggest that miR-124 acts as a tumor-suppressor and a modulator of energy metabolism through a PTB1/PKM1/PKM2 feedback cascade in human colorectal tumor cells.
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; Department of General and Gastroenterological Surgery, Osaka Medical College, 2-7 Daigaku-machi, 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, 1-1 Yanagido, 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, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Minami
authors.initials: M
authors.lastname: Kumazaki
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Shinohara
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Nami
authors.initials: N
authors.lastname: Yamada
authors.affiliation: Department of Gastroenterology, Fujita Health University, School of Medicine, 1-98 Dengakugakubo Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Department of Anatomy and Cell Biology, Division of Life Sciences, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Anatomy and Cell Biology, Division of Life Sciences, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Otsuki
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Bunji
authors.initials: B
authors.lastname: Uno
authors.affiliation: Department of General and Gastroenterological Surgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Uchiyama
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan. Electronic address: yakao@gifu-u.ac.jp.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Akao
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D004734:Energy Metabolism; D025461:Feedback, Physiological; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D020413:3' Untranslated Regions; D002352:Carrier Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D008565:Membrane Proteins; D035683:MicroRNAs; D038941:Polypyrimidine Tract-Binding Protein; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins; C509207:MIRN124 microRNA, human; C450006:PTBP1 protein, human
keywords: Colorectal cancer; PKM; PTB1; Warburg effect; miR-124