Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Positive feedback of DDX6/c-Myc/PTB1 regulated by miR-124 contributes to maintenance of the Warburg effect in colon cancer cells. 2614 48

Pyruvate kinase isoenzyme M2 (PKM2) has previously been identified as a tumor biomarker and potential therapeutic target for the treatment of cancer. In the present study, FFJ-3, a structurally modified version of mollugin, an extract of the Traditional Chinese herbal medicine Rubia tinctorum (madder) was used in order to determine the anticancer activity of the compound and investigate the potential mechanisms underlying this effect in human cancer cells. The results of the present study revealed that FFJ-3 inhibited the survival of HepG2 human hepatoma cells, MCF-7 human breast cancer cells and A549 human lung adenocarcinoma cells using the MTT assay. In addition, FFJ-3 arrested cell cycle progression at G2/M and G1 in HepG2 and A549 cells, respectively. Further analyses demonstrated that FFJ-3 attenuated the expression of PKM2 protein via the inhibition of the phosphoinositide 3-kinase (PI3K)/Akt serine/threonine kinase (Akt) signaling pathway. Furthermore, treatment of all three cell types with FFJ-3 significantly increased apoptosis and decreased the mitochondrial membrane potential compared with the untreated control group. In addition, FFJ-3 treatment increased the ratio of B-cell lymphoma-2 (Bcl-2)/Bcl-2 associated X and activated the caspase-3 cascade. In conclusion, the inhibition of the PI3K/Akt signaling pathway and activation of the caspase-3 cascade by FFJ-3 were primarily responsible for the inhibition of cell proliferation and induction of apoptosis in MCF-7, HepG2 and A549 cells. The results of the present study suggest a potential therapeutic role for FFJ-3 in the treatment of human cancer.
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PMID:FFJ-3 inhibits PKM2 protein expression via the PI3K/Akt signaling pathway and activates the mitochondrial apoptosis signaling pathway in human cancer cells. 2845 40