The human DEAD/H-box
RNA helicase gene DDX6 is a target of the t(11;14)(q23;q32)
chromosomal translocation observed in human
B-cell lymphoma, and the overexpression of its
protein has been shown to cause malignant transformation. DDX6 has a variety of functions such as translation initiation,
pre-mRNA splicing, ribosome assembly, and more. However, details of the regulatory mechanism of DDX6 and functions of DDX6 in
cancer cells are largely unknown. On the other hand, the Warburg effect is a well-known feature of
cancer cells.
Pyruvate kinase in muscle (PKM), which is a rate-limiting glycolytic
enzyme, has 2
isoforms, PKM1 and PKM2. It has been frequently reported that PKM2 is a
tumor-specific
isoform and promotes the Warburg effect. However, the functions of the PKM1 gene have been hardly mentioned. Here, we showed that DDX6 was overexpressed in
colorectal cancer specimens and regulated by
microRNA (miR)-124 in
colon cancer cells. Also, a DDX6/c-Myc/PTB1 positive feedback circuit regulated by miR-124 was shown to be established and to contribute to maintenance of the Warburg effect. Moreover, we showed that knockdown of DDX6 induced mainly apoptosis through an imbalance of PKM gene expression, especially causing down-regulation of PKM1 in
colon cancer cells. These results suggest that miR-124 is a fine tuner of the Warburg effect and that DDX6 is one of the key molecules in Warburg effect-related miR-124 targeting various genes.