Aerobic glycolysis (the Warburg effect) facilitates tumor growth, and drugs targeting aerobic glycolysis are being developed. However, how the Warburg effect is directly regulated is largely unknown. Here we show that transcription factor SIX1 directly increases the expression of many glycolytic genes, promoting the Warburg effect and tumor growth in vitro and in vivo. SIX1 regulates glycolysis through HBO1 and AIB1 histone acetyltransferases. Cancer-related SIX1 mutation increases its ability to promote aerobic glycolysis and tumor growth. SIX1 glycolytic function is directly repressed by microRNA-548a-3p, which is downregulated, inversely correlates with SIX1, and is a good predictor of prognosis in breast cancer patients. Thus, the microRNA-548a-3p/SIX1 axis strongly links aerobic glycolysis to carcinogenesis and may become a promising cancer therapeutic target.

Summary:Purpose: Two earlier population-based studies provide conflicting information on the association between low socioeconomic status (SES) and risk for epilepsy. Seizure etiologies (e.g., head injury, stroke) associated with low SES were not addressed in prior analyses. We assess the relation between SES indices and incident epilepsy separately for children and adults and in subgroups defined by seizure etiology.Methods: In this population-based case-control study, a surveillance system identified incident unprovoked seizure or first diagnosis of epilepsy throughout Iceland (n = 418). Controls were selected from the population registry as the next two same-sex births alive, residing in Iceland at the time of the index seizure, and without a history of unprovoked seizure on the date of the case's incident seizure (n = 835). The odds ratio measured the association between SES and epilepsy.Results: An association was found between epilepsy and SES among adults, but not among children. Among adults, low education was associated with an increased risk for epilepsy [odds ratio (OR), 2.29; 95% confidence interval (CI), 1.21-4.34), and home ownership was protective (OR, 0.63; 95% CI, 0.43-0.92). When analyses were repeated by seizure etiology, this association remained only in the group with epilepsy of unknown cause, even after adjusting for alcohol consumption.Conclusions: Low SES, indexed by low education or lack of home ownership, is a risk factor for epilepsy in adults, but not in children, suggesting a cumulative effect of SES on risk for epilepsy. This association is not explained by established risk factors for epilepsy (e.g., head injury, stroke). We find no evidence of a downward social drift among cases whose parents had epilepsy.

ADAMTS-5 was identified as a novel direct target of miR-30a. IL-1β suppresses miR-30a expression through activation of AP-1 (c-jun/c-fos). AP-1/miR-30a is essential for IL-1β-induced ADAMTS-5 upregulation in OA. Downregulation of miR-30a in OA is negatively correlated with ADAMTS-5 expression.

Runx2 was identified as a novel direct target of miR-105. FGF2 inhibits miR-105 transcription through recruitment of p65 to miR-105 promoter. p65/miR-105 is essential for FGF2-mediated Runx2 and ADAMTS upregulation. miR-105 is downregulated in OA and inversely correlated with Runx2 expression.

The role of the innate immune protein LGP2 (laboratory of genetics and physiology 2) in FMDV-infected cells remains unknown. Here, we demonstrate the antiviral role of LGP2 during FMDV infection. FMDV infection triggered LGP2 mRNA expression but reduced protein expression. Overexpression of LGP2 suppressed FMDV replication, and the inflammatory response was significantly inhibited by LGP2 in virus-infected cells. The N-terminal DExDc and the C-terminal regulatory domain regions of LGP2 were essential for LGP2-mediated antiviral activity against FMDV. Disruption of RNA recognition by LGP2 is suggested to abolish completely LGP2-mediated antiviral activity against FMDV. FMDV leader protein (Lpro), as well as the 3Cpro and 2B proteins were determined to possess the ability to induce reduction of LGP2 protein expression. 2B-induced reduction of LGP2 was independent of cleavage of eukaryotic translation initiation factor 4 gamma; and the proteasomes, lysosomes or caspase-dependent pathways were not involved in this process. The C-terminal amino acids of 101–154 were essential for 2B-induced reduction of LGP2 and upregulation of inflammatory response. Direct interaction was demonstrated between LGP2 and 2B. Our results describe the antiviral role of LGP2 against FMDV and a novel antagonistic mechanism of FMDV that is mediated by 2B protein.