The negative interplay between Aurora A/B and BRCA1/2 controls cancer cell growth and tumorigenesis via distinct regulation of cell cycle progression, cytokinesis, and tetraploidy

It is well known that the activation of Aurora A/B (Aur A/B) or inactivation of BRCA1/2 induces tumor formation. Others and we have reported that the mutual suppression between Aur A/B and BRCA1/2 may manipulate cancer cell growth and tumorigenesis, however, the interactive regulation and mechanism between these molecules are still elusive. In this study, by consecutive silencing of Aur A/B or/and BRCA1/2 with specific shRNAs, we showed that, in BRCA2-deficient pancreatic cancer cell line Capan-1 and in ovarian cancer cell line OVCA433, Aur A/B and BRCA1/2 inversely regulated the expression of each other likely through proteasome-mediated proteolysis but not through gene transcription. Aur A/B and BRCA1/2 conversely regulated cell cycle progression mainly through control of p53 and cyclin A. Moreover, the disruption of Aur A/B blocked abnormal cytokinesis and decreased cell multinuclearity and chromosome tetraploidy, whereas the deprivation of BRCA1/2 promoted the abnormal cytokinesis and enhanced the cell multinuclearity and tetraploidy. Furthermore, we showed by animal assays that the depletion of Aur A/B inhibited tumor growth of both cell lines, while the knockdown of BRCA1/2 promoted the tumor growth. However, the concurrent silencing of Aur A/B and BRCA1/2 diminished the effects of these molecules on the regulation of cell cycle, cytokinesis, and tetraploidy, leading to the burdened tumor sizes similar to those induced by scrambled shRNA-treated control cells. In summary, our study revealed that the negative interplay between Aur A/B and BRCA1/2 inversely controls the cell proliferation, cell cycle progression, cell multinuclearity, and tetraploidization to modulate tumorigenesis

Clinical research in ovarian cancer: consensus recommendations from the Gynecologic Cancer InterGroup

The Gynecologic Cancer InterGroup (GCIG) sixth Ovarian Cancer Conference on Clinical Research was held virtually in October, 2021, following published consensus guidelines. The goal of the consensus meeting was to achieve harmonisation on the design elements of upcoming trials in ovarian cancer, to select important questions for future study, and to identify unmet needs. All 33 GCIG member groups participated in the development, refinement, and adoption of 20 statements within four topic groups on clinical research in ovarian cancer including first line treatment, recurrent disease, disease subgroups, and future trials. Unanimous consensus was obtained for 14 of 20 statements, with greater than 90% concordance in the remaining six statements. The high acceptance rate following active deliberation among the GCIG groups confirmed that a consensus process could be applied in a virtual setting. Together with detailed categorisation of unmet needs, these consensus statements will promote the harmonisation of international clinical research in ovarian cancer

Impact of Nitrite Supplementation on Bioactive Peptides during Sausage Processing

The goal of this investigation was to examine the impact of nitrite supplementation on the concentration, antioxidant properties, and species of antioxidant peptides in fermented sausages. The polypeptide concentration in nitrite-supplemented sausages was markedly elevated during sausage processing compared to the blank control (p p p < 0.05). Based on the liquid chromatograph-mass spectrometer (LC-MS) analysis of the sausage, LPGGGHGDL, TKYRVP, FLKMN, SAGNPN, GLAGA, LPGGGT, DLEE, GKFNV, GLAGA, AEEEYPDL, HCNKKYRSEM, TSNRYHSYPWG, and other polypeptides exhibited antioxidant properties. Moreover, the number of species of antioxidant polypeptides in the nitrite-supplemented sausage was greater in comparison to the controls. Based on this evidence, it may be concluded that nitrite supplementation positively modulated antioxidant polypeptide formation in fermented sausages, thereby providing strong evidence that nitrite supplementation significantly enhances sausage quality

Impact of Nitrite Supplementation on Bioactive Peptides during Sausage Processing

The goal of this investigation was to examine the impact of nitrite supplementation on the concentration, antioxidant properties, and species of antioxidant peptides in fermented sausages. The polypeptide concentration in nitrite-supplemented sausages was markedly elevated during sausage processing compared to the blank control (p &lt; 0.05). Moreover, nitrite supplementation in fermented sausages markedly enhanced the DPPH, as well as the ABTS, hydroxyl radical, and superoxide anion free radical scavenging abilities (FRSA) of polypeptides (p &lt; 0.05). The ferrous ion chelating ability was also significantly enhanced (p &lt; 0.05). Based on the liquid chromatograph-mass spectrometer (LC-MS) analysis of the sausage, LPGGGHGDL, TKYRVP, FLKMN, SAGNPN, GLAGA, LPGGGT, DLEE, GKFNV, GLAGA, AEEEYPDL, HCNKKYRSEM, TSNRYHSYPWG, and other polypeptides exhibited antioxidant properties. Moreover, the number of species of antioxidant polypeptides in the nitrite-supplemented sausage was greater in comparison to the controls. Based on this evidence, it may be concluded that nitrite supplementation positively modulated antioxidant polypeptide formation in fermented sausages, thereby providing strong evidence that nitrite supplementation significantly enhances sausage quality.</jats:p

MS: Wip1 suppresses angiogenesis through the STAT3-VEGF signalling pathway in serous ovarian cancer

Abstract Multifaceted functions of the so-called “oncogene” Wip1 have been reported in a previous study, while its actual role remains to be explored in serous ovarian cancer (SOC). In this study, by performing bioinformatic analysis with a public database and immunohistochemical staining of Wip1 in tumour tissue from SOC, we concluded that decreased expression of Wip1 was associated with a higher rate of tumour metastasis and platinum-based therapy resistance and increased ascites volume, which led to poorer prognosis in SOC patients. We also found that overexpression of Wip1 in SKOV3 cells decreased the levels of several cytokines, including VEGF, by secretome profiling analysis, and Wip1 overexpression suppressed angiogenesis both in vitro and in vivo. Mechanistic studies indicated that overexpression of Wip1 decreased the expression of VEGF at both the protein and mRNA levels and that the inhibitory effect was mediated by dephosphorylation of STAT3 at Ser727. Our study uncovered the role of Wip1 in SOC and provides a novel therapeutic strategy for suppressing angiogenesis

Wip1 suppresses angiogenesis through the STAT3-VEGF signalling pathway in serous ovarian cancer

AbstractMultifaceted functions of the so-called “oncogene” Wip1 have been reported in a previous study, while its actual role remains to be explored in serous ovarian cancer (SOC). In this study, by performing bioinformatic analysis with a public database and immunohistochemical staining of Wip1 in tumour tissue from SOC, we concluded that decreased expression of Wip1 was associated with a higher rate of tumour metastasis and platinum-based therapy resistance and increased ascites volume, which led to poorer prognosis in SOC patients. We also found that overexpression of Wip1 in SKOV3 cells decreased the levels of several cytokines, including VEGF, by secretome profiling analysis, and Wip1 overexpression suppressed angiogenesis both in vitro and in vivo. Mechanistic studies indicated that overexpression of Wip1 decreased the expression of VEGF at both the protein and mRNA levels and that the inhibitory effect was mediated by dephosphorylation of STAT3 at Ser727. Our study uncovered the role of Wip1 in SOC and provides a novel therapeutic strategy for suppressing angiogenesis.</jats:p