Energy metabolism is significantly reprogrammed in many human cancers, and these alterations confer many advantages to cancer cells, including the promotion of biosynthesis, ATP generation, detoxification and support of rapid proliferation. The pentose phosphate pathway (PPP) is a major pathway for glucose catabolism. The PPP directs glucose flux to its oxidative branch and produces a reduced form of nicotinamide adenine dinucleotide phosphate (NADPH), an essential reductant in anabolic processes. It has become clear that the PPP plays a critical role in regulating cancer cell growth by supplying cells with not only ribose-5-phosphate but also NADPH for detoxification of intracellular reactive oxygen species, reductive biosynthesis and ribose biogenesis. Thus, alteration of the PPP contributes directly to cell proliferation, survival and senescence. Furthermore, recent studies have shown that the PPP is regulated oncogenically and/or metabolically by numerous factors, including tumor suppressors, oncoproteins and intracellular metabolites. Dysregulation of PPP flux dramatically impacts cancer growth and survival. Therefore, a better understanding of how the PPP is reprogrammed and the mechanism underlying the balance between glycolysis and PPP flux in cancer will be valuable in developing therapeutic strategies targeting this pathway.

The inflammasome has an essential function in innate immune, responding to a wide variety of stimuli. Here we show that the lncRNANeat1promotes the activation of several inflammasomes.Neat1associates with the NLRP3, NLRC4, and AIM2 inflammasomes in mouse macrophages to enhance their assembly and subsequent pro-caspase-1 processing.Neat1also stabilizes the mature caspase-1 to promote interleukin-1β production and pyroptosis. Upon stimulation with inflammasome-activating signals,Neat1, which normally resides in the paraspeckles, disassociates from these nuclear bodies and translocates to the cytoplasm to modulate inflammasome activation using above mechanism.Neat1is also up-regulated under hypoxic conditions in a HIF-2α-dependent manner, mediating the effect of hypoxia on inflammasomes. Moreover, in the mouse models of peritonitis and pneumonia,Neat1deficiency significantly reduces inflammatory responses. These results reveal a previously unrecognized role of lncRNAs in innate immunity, and suggest thatNeat1is a common mediator for inflammasome stimuli.

Survivin is a member of the inhibitor of apoptosis protein (IAP) family that has been implicated in both apoptosis inhibition and cell cycle control. However, its inhibitory mechanism and subcellular localization remain controversial. In this report, we provided evidence for the first time that Survivin physically interacts with Smac/DIABLO both in vitro and in vivo. A point mutation (D71R) in the baculovirus IAP repeat motif and a C-terminal deletion mutant (Surv-BIR) of Survivin fail to bind to Smac/DIABLO and abrogate its ability to inhibit apoptosis. The N-terminal of mature Smac/DIABLO is absolutely required for Survivin·Smac complex formation. Subcellular distributions of Survivin and Smac/DIABLO showed that they co-localized within the cytosol during interphase. In addition, Survivin was found to be incapable of binding to caspase. We also identified that the co-presence of Smac/DIABLO and XIAP was required for Survivin to inhibit caspase cleavage in a cell-free system. In conclusion, our results provide the first evidence that the interaction between Smac/DIABLO and Survivin is an essential step underling the inhibition of apoptosis induced by Taxol.