Glioma stem cells (GSC) are a subpopulation of tumor cells with special abilities to proliferate and differentiate in gliomas. They are one of the main causes of tumor recurrence, especially under hypoxic conditions. Although long noncoding RNAs (lncRNA) are known to be involved in numerous biological processes and are implied in the occurrence of certain diseases, their role in tumor development and progression remains poorly understood. Here we explored the mechanisms by which lncRNA derived from hypoxic GSCs (H-GSC) cause glioma progression. Isolation and identification of the Linc01060 gene, the exosomes containing them, and the proteins from tumor cells regulating the gene allowed for studying the effects of Linc01060 on proliferation and glycometabolism. H-GSC exerted their effects by transferring exosomes to glioma cells, resulting in a significant increase in Linc01060 levels. Mechanistically, Linc01060 directly interacted with the transcription factor myeloid zinc finger 1 (MZF1) and enhanced its stability. Linc01060 facilitated nuclear translocation of MZF1 and promoted MZF1-mediated c-Myc transcriptional activities. In addition, c-Myc enhanced the accumulation of the hypoxia-inducible factor-1 alpha (HIF1a) at the posttranscriptional level. HIF1a bound the hormone response elements of the Linc01060 promoter, upregulating the transcription of Linc01060 gene. Clinically, Linc01060 was upregulated in glioma and was significantly correlated with tumor grade and poor clinical prognosis. Overall, these data show that secretion of Linc01060-containing exosomes from H-GSCs activates prooncogenic signaling pathways in glioma cells to promote disease progression.Significance: These findings suggest that inhibition of Linc01060containing exosomes or targeting the Linc01060/MZF1/c-Myc/ HIF1a axis may be an effective therapeutic strategy in glioma.
The classical tests of general relativity -light deflection, time delay and perihelion shift -are applied, along with the geodetic precession test, to the five-dimensional extension of the theory known as Kaluza-Klein gravity, using an analogue of the four-dimensional Schwarzschild metric. The perihelion advance and geodetic precession calculations are generalized for the first time to situations in which the components of momentum and spin along the extra coordinate do not vanish. Existing data on light-bending around the Sun using long-baseline radio interferometry, ranging to Mars using the Viking lander, and the perihelion precession of Mercury all constrain a small parameter b associated with the extra part of the metric to be less than |b| < 0.07 in the solar system. An order-of-magnitude increase in sensitivity is possible from perihelion precession, if better limits on solar oblateness become available. Measurement of geodetic precession by the Gravity Probe B satellite will improve this significantly, probing values of b with an accuracy of one part in 10 4 or more.
A 5 D Machian generalization of Einstein's theory of gravitation is described in which the cosmological constant appears as the contribution of the rest of the universe to the gravitational field of an "isolated" source. This work amounts to a Machian interpretation of the Kaluza-Klein theory.The standard cosmological models are derived in this framework. and it is shown thatin conformity with the interpretation presented herethe cosmological constant does not directly contribute to the geometric description of the universe as a whole.
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