One of the principal biochemical characteristics of malignant cells compared to normal cells is a metabolic switch from oxidative phosphorylation to increased glycolysis, even under hypoxic conditions, and is termed the Warburg effect. Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate and is considered to be a key checkpoint of anaerobic glycolysis. It is elevated in many types of cancers and has been linked to tumor growth, maintenance, and invasion; therefore, its inhibition may restrict the energy supply in tumors and thereby reduce the metastatic and invasive potential of cancer cells. This enzyme is receiving a great deal of attention as a potential diagnostic marker or a predictive biomarker for many types of cancer and as a therapeutic target for new anticancer treatments. In this review, we summarize the role of LDHA in cancer, discuss its potential significance in clinical diagnosis and prognosis of cancer, and propose LDHA as a novel target for the inhibition of tumor growth and invasiveness. V C 2013 IUBMB Life, 65(11): [904][905][906][907][908][909][910] 2013
High-temperature (high-T c ) superconductivity appears as a consequence of the carrier-doping of an undoped parent compound exhibiting antiferromagnetic order; thereby, ground-state properties of the parent compound are closely relevant to the superconducting state 1,2 . On the basis of the concept, a spin-fluctuation has been addressed as an origin of pairing of the superconducting electrons in cuprates 1 . Whereas, there is growing interest in the pairing mechanism such as an unconventional spin-fluctuation or an advanced orbital-fluctuation due to the characteristic multi-orbital system in iron-pnictides 3-6 . Here, we report the discovery of an antiferromagnetic order as well as a unique structural transition in electron-overdoped
MicroRNAs (miRNAs) are non-coding small RNAs that function as negative regulators of gene expression involving in the tumor biology. ATP citrate lyase (ACLY), a key enzyme initiating de novo lipid synthesis, has been found to be upregulated in cancer cells, and its inhibition causes suppressive effects in a variety of tumors. At present, although several ACLY inhibitors have been reported, the potential role of miRNAs in interfering ACLY still needs further clarification. Herein, four different types of tumor cells including osteosarcoma, prostate, cervical and lung cancers were adopted in our study, and we have demonstrated that miR-22 directly downregulated ACLY. Moreover, miR-22 was proved to attenuate cancer cell proliferation and invasion, as well as promote cell apoptosis via inhibiting ACLY. Additionally, we confirmed the higher ACLY protein levels and the lower miR-22 expressions in hundreds of clinical samples of the four primary tumors, and a negative correlation relationship between ACLY and miR-22 was clarified. Finally, in the four animal models, we found that along with the loss of the ACLY expression, the miR-22-treated mice developed rather smaller tumors, less probabilities of distant metastasis, and fairly longer survivals. De novo lipogenesis suppression triggered by miR-22-ACLY axis may contribute to the inhibition of tumor growth and metastasis. These findings provide unequivocal proofs that miR-22 is responsible for the posttranscriptional regulation of ACLY, which yields promising therapeutic effects in osteosarcoma, prostate, cervical and lung cancers.
Background:The protein-serine/threonine kinase PIM2 regulates glycolysis, but the mechanism is not fully elucidated. Results: PIM2 interacts with PKM2 and phosphorylates PKM2 on the Thr-454 residue. Conclusion: This phosphorylation of PKM2 increases glycolysis and proliferation in cancer cells. Significance: PIM2-dependent phosphorylation of PKM2 is critical for regulating the Warburg effect in cancer, highlighting PIM2 as a potential therapeutic target.
Perovskite PbCoO synthesized at 12 GPa was found to have an unusual charge distribution of PbPbCoCoO with charge orderings in both the A and B sites of perovskite ABO. Comprehensive studies using density functional theory (DFT) calculation, electron diffraction (ED), synchrotron X-ray diffraction (SXRD), neutron powder diffraction (NPD), hard X-ray photoemission spectroscopy (HAXPES), soft X-ray absorption spectroscopy (XAS), and measurements of specific heat as well as magnetic and electrical properties provide evidence of lead ion and cobalt ion charge ordering leading to PbPbCoCoO quadruple perovskite structure. It is shown that the average valence distribution of PbCoO between PbCrO and PbNiO can be stabilized by tuning the energy levels of Pb 6s and transition metal 3d orbitals.
Rheumatoid arthritis is an autoimmune disease that primarily affects the limbs, but the pathogenic mechanism remains unclear. cd T cells, a T-cell subpopulation, are characterized by multiple biological functions and associated with a variety of diseases. This study investigated the antigen-presenting effects of cd T cells and their relationship with rheumatoid arthritis development. We found that Vc9Vd2 T cells (the predominant subtype of cd T cells in peripheral blood) were activated by isopentenyl pyrophosphate to continuously proliferate and differentiate into effector memory cells. The effector memory Vc9Vd2 T cells exhibited phenotypic characteristics of specific antigen-presenting cells, including high HLA-DR and CD80/86 expression. These Vc9Vd2 T cells could present soluble antigens and synthetic peptides to CD41 T cells. Vc9Vd2 T cells with different phenotypes showed different cytokine secretion patterns. Effector memory Vc9Vd2 T cells simultaneously secreted not only interferon (IFN)-c but also IL-17. The peripheral blood and joint synovial fluid from RA patients contained numerous heterogeneous cd T cells that were predominantly effector memory Vc9Vd2 T cells with the ability to secrete inflammatory factors. We also found that cd T cells had a similar antigen-presenting capability to B cells. These results suggest that during the development of rheumatoid arthritis, cd T cells can aggravate immune dysfunction and produce abnormal immune damage by secreting cytokines and inducing inflammatory cells to participate in synergistic inflammatory responses. Furthermore, cd T cells can behave similarly to B cells to present viral peptides and autoantigen peptides to CD4 1 T cells, thus sustaining CD4 1 T-cell activation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.