Cycles of solar ultraviolet radiation favor periodic expansions of cyanobacterial blooms in global lakes.

Global warming and eutrophication are known to increase the prevalence of cyanobacterial blooms, posing a severe threat to the ecological stability and sustainability of water bodies. The long-term (over an annual time frame) effect of UV radiation on cyanobacterial blooms in lakes are rarely discussed though the substantial effects of high-intensity UV radiation on the growth inhibition of marine phytoplankton were studied. Here, we employed the datasets on surface solar UV radiation, nitrogen and phosphorus concentrations, and the annual scales and frequencies of cyanobacterial blooms in lakes across long-term spatial scales to probe the relationship of UV radiation with cyanobacterial blooms. The results indicated that enhanced solar UV radiation may unintentionally stimulate cyanobacterial growth and favor the expansions of cyanobacterial blooms in lakes around the world. The fluctuating UV radiation significantly affects the annual scales of cyanobacterial blooms in both eutrophic and oligotrophic lakes. Solar UV radiation enhances the positive impact of rising phosphorus levels on cyanobacterial blooms because UV radiation prompts the synthesis of polyphosphate in cyanobacteria cells, which helps cyanobacteria to alleviate the stress of UV light. The scales of cyanobacterial blooms are significantly impacted by solar UV radiation intensities as opposed to the annual frequency of cyanobacterial blooms. Furthermore, solar UV radiation fluctuation with a 9-year period over a 14-year main cycles significantly affects the periodicities of cyanobacterial blooms in global lakes, which provides a basis for predicting the peak value of the scales of cyanobacterial blooms in lakes. These findings opened up new avenues of inquiry into the mechanism and management strategies of cyanobacterial blooms in lakes worldwide.

Golgi phosphoprotein 3 promotes glioma progression via inhibiting Rab5-mediated endocytosis and degradation of epidermal growth factor receptor.

BACKGROUND: Golgi phosphoprotein 3 (GOLPH3) is associated with worse prognosis of gliomas, but its role and mechanism in glioma progression remain largely unknown. This study aimed to explore the role and mechanism of GOLPH3 in glioma progression. METHODS: The expression of GOLPH3 in glioma tissues was detected by quantitative PCR, immunoblotting, and immunohistochemistry. GOLPH3's effect on glioma progression was examined using cell growth assays and an intracranial glioma model. The effect of GOLPH3 on epidermal growth factor receptor (EGFR) stability, endocytosis, and degradation was examined by immunoblotting and immunofluorescence. The activity of Rab5 was checked by glutathione S-transferase pulldown assay. RESULTS: GOLPH3 was upregulated in gliomas, and its downregulation inhibited glioma cell proliferation both in vitro and in vivo. Furthermore, GOLPH3 depletion dampened EGFR signaling by enhancing EGFR endocytosis, driving EGFR into late endosome and promoting lysosome-mediated degradation. Interestingly, GOLPH3 bound to Rab5 and GOLPH3 downregulation promoted the activation of Rab5. In addition, Rab5 depletion abolished the effect of GOLPH3 on EGFR endocytosis and degradation. CONCLUSION: Our results imply that GOLPH3 promotes glioma cell proliferation via inhibiting Rab5-mediated endocytosis and degradation of EGFR, thereby activating the phosphatidylinositol-3 kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway. We find a new mechanism by which GOLPH3 promotes tumor progression through regulating cell surface receptor trafficking. Extensive and intensive understanding of the role of GOLPH3 in glioma progression may provide an opportunity to develop a novel molecular therapeutic target for gliomas.

GOLPH3 promotes glioblastoma cell migration and invasion via the mTOR-YB1 pathway in vitro.

The identification of genes involved in carcinogenesis and tumor progression is of great interest, since these genes might be possible as candidates for new tumor targeted therapy strategies. Our previous study shows that Golgi phosphoprotein 3 (GOLPH3) is involved in glioma cell migration and invasion, the critical characteristics of malignant gliomas. In this study, we explored the mechanism of GOLPH3 affecting cell migration and invasion and found that GOLPH3 promotes glioblastoma (GBM) cell migration and invasion via the mammalian target of rapamycin(mTOR)-Y-box binding protein-1 (YB1) pathway in vitro. Both the protein levels of GOLPH3 and YB1 were up-regulated in human glioma tissues and they exhibited direct correlation with each other. In addition, down-regulation of GOLPH3 inhibited glioma cell migration and invasion, while over-expression of GOLPH3 enhanced them. Meanwhile, GOLPH3 down-regulation led to a significant decrease of YB1 level as well as mTOR activity, both required for glioma cell migration and invasion. On the contrary, YB1 level and mTOR activity increased after GOLPH3 over-expression. YB1 down-regulation or mTOR ATP site inhibitor INK128 treatment inhibited cell migration and invasion, similar to the effect of GOLPH3 down-regulation. Furthermore, over-expression of GOLPH3 induced glioma cell migration and invasion was blocked by INK128 and YB1 down-regulation. Taken together, these results show that GOLPH3 promotes glioblastoma cell migration and invasion via the mTOR-YB1pathway, indicating that GOLPH3-mTOR-YB1 pathway might be a new therapeutic target for glioma treatment.

Geranylgeranyltransferase I regulates HIF-1α promoting glioblastoma cell migration and invasion.

Glioblastoma multiforme is a highly migratory and invasive brain tumor in which hypoxia inducible factor-1α (HIF-1α) plays important roles. However, the underlying mechanisms regulating the action of HIF-1α in glioma cell migration and invasion ability remain unclear. We reported here that HIF-1α was regulated by geranylgeranyltransferase I (GGTI), a protein prenylation transferase, and then promoted glioma cell migration and invasion. The migratory and invasive ability of glioma cells were enhanced by hypoxia treatment but inhibited by down-regulation of HIF-1α. GGTI activity inhibition or GGTI specific ß subunit (GGTI ß) knocking-down decreased HIF-1α protein level. In addition, down-regulation of GGTI ß inhibited migration and invasion of glioma cells under hypoxia, while GGTI ß over-expression promoted it. Furthermore, the effect of GGTI ß over-expression on cell migration and invasion was abolished by HIF-1α down-regulation. In summary, our study showed, for the first time, that HIF-1α was regulated by protein prenylation transferase GGTI and mediated the effect of GGTI on glioma cell migration and invasion.

GOLPH3 regulates the migration and invasion of glioma cells though RhoA.

Golgi phosphoprotein 3 (GOLPH3) has been reported to be involved in the development of several human cancers. However, the biological significance of GOLPH3 in glioma progression remains largely unknown. In this study, we report, for the first time, that downregulation of GOLPH3 led to clear reductions in glioma cell migration and invasion. In addition, downregulation of GOLPH3 inhibited the expression of the small GTPase RhoA as well as cytoskeletal reorganization, which are both required for glioma cell migration. Furthermore, we found that the observed reductions in glioma cell migration and RhoA level could be rescued by RhoA overexpression. Taken together, these results show that GOLPH3 contributes to the motility of glioma cells by regulating the expression of RhoA.