miR-124, miR-137 and miR-340 regulate colorectal cancer growth via inhibition             of the Warburg effect.
Colorectal cancer represents one of the most challenging diseases. Increasing             evidence indicates that aberrant expression of microRNAs (miRNAs) is related to             pathogenesis of colorectal cancer. Cancer cells reprogram metabolic pathways to             sustain higher proliferation rates. Whether mechanisms underlying the role of             miRNA in colorectal cancer are involved in metabolic reprogramming and the mechanisms             through which miRNAs alter cancer metabolism are as yet unknown. Herein, we show             that miR-124, miR-137 and miR-340 are associated with poor prognosis of colorectal             cancer. Expression of these miRNAs inhibits the growth of colorectal cancer cells.             PKM (pyruvate kinase isozyme) alternative splicing proteins (PTB1/hnRNAPA1/hnRNAPA2),             which control the inclusion of exon 9 (PKM1) or exon 10 (PKM2), are targeted by             miR-124, miR-137 and miR-340. Consequently, miR-124, miR-137 and miR-340 switch             PKM gene expression from PKM2 to PKM1. High ratios of PKM1/PKM2 inhibit the glycolysis             rate, but elevate the glucose flux into oxidative phosphorylation. These results             demonstrate that miRNAs (miR-124, miR-137 and miR-340) impair colorectal cancer             growth by counteracting the Warburg effect due to regulating alternative splicing             of the PKM gene.
Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China.
Yan
Y
Sun
Xiaoping
X
Zhao
Yuhong
Y
Zhou
Yu
Y
Hu
D017398:Alternative Splicing; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D010766:Phosphorylation; D011379:Prognosis; D011770:Pyruvate Kinase / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism; D000097810:Thyroid Hormone-Binding Proteins
D002352:Carrier Proteins; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D008565:Membrane Proteins; D035683:MicroRNAs; D011770:Pyruvate Kinase; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins; C509207:MIRN124 microRNA, human; C545567:MIRN137 microRNA, human; C570046:MIRN340 microRNA, human; C439768:hnRNP A2