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Background: The risks of cardiovascular disease (CVD) and CVD mortality are prevalent among cancer survivors (CS) population. The 2022 ESC Guidelines on cardio‐oncology have recommended that modifying cardiovascular risk factors (CVRF) could potentially improve long‐term outcomes in CS. Objectives: To identify the independent and joint chronic kidney disease (CKD) associations of hyperuricemia with the incidence of CVD and mortality outcomes among CS. Methods: Utilizing data from the US National Health and Nutrition Examination Survey spanning 2005–2018, we assessed the risk of CVD through weighted multivariable logistic regression and restricted cubic spline (RCS) regression. Additionally, all‐cause and CVD‐related mortality were evaluated using weighted multivariable Cox regression and Kaplan–Meier analysis. Subgroup analysis was conducted to further elucidate the interplay between hyperuricemia, CKD, and mortality within the CS population. Results: A total of 3276 CS participants were enrolled in this study. Results showed that hyperuricemia was positively related to the incidence of CVD (OR [95% CI] = 1.86 [1.24, 2.81], p = 0.004). RCS analysis further demonstrated that uric acid levels ≥345 μmol/L positively correlated with CVD incidence (p value for nonlinearity = 0.0013). However, the association between hyperuricemia and CVD mortality, as well as all‐cause mortality did not reach statistical significance in the fully adjusted model (HR = 1.48, 95% CI: 0.92–2.39, p = 0.11; HR = 1.11, 95% CI:0.92, 1.34, p = 0.28, respectively). Among CS participants with CKD, hyperuricemia could increase risks of all‐cause (HR [95% CI] = 1.39 [1.08, 1.11], p = 0.02) and CVD mortality (HR [95% CI] =2.17 [1.29, 3.66], p = 0.004) after adjusting for sex, age, and ethnicity. Conclusions: In the CS population, hyperuricemia was positively associated with the incidence of CVD. In addition, CKD might be an intermediate variable among the CS population that mediated the effects of hyperuricemia on mortality. [ABSTRACT FROM AUTHOR]

Background: Liver cancer is a highly malignant disease and the third leading cause of cancer death worldwide. Abnormal activation of PI3K/Akt signaling is common in cancer, but whether phosphoinositide‐3‐kinase regulatory subunit 3 (PIK3R3) plays a role in liver cancer is largely unexplored. Methods: We determined the expression of PIK3R3 in liver cancer by using TCGA data and our clinical samples and knocked it down by siRNA or overexpressing it by the lentivirus vector system. We also investigated the function of PIK3R3 by colony formation, 5‐Ethynyl‐2‐Deoxyuridine, flow cytometry assay, and subcutaneous xenograft model. The downstream of PIK3R3 was explored by RNA sequence and rescue assays. Results: We found that PIK3R3 was significantly upregulated in liver cancer and correlated with prognosis. PIK3R3 promoted liver cancer growth in vitro and in vivo by controlling cell proliferation and cell cycle. RNA sequence revealed that hundreds of genes were dysregulated upon PIK3R3 knockdown in liver cancer cells. CDKN1C, a cyclin‐dependent kinase inhibitor, was significantly upregulated by PIK3R3 knockdown, and CDKN1C siRNA rescued the impaired tumor cell growth. SMC1A was partially responsible for PIK3R3 regulated function, and SMC1A overexpression rescued the impaired tumor cell growth in liver cancer cells. Immunoprecipitation demonstrated there is indirect interaction between PIK3R3 and CNKN1C or SMC1A. Importantly, we verified that PIK3R3‐activated Akt signaling determined the expression of CDKN1C and SMC1A, two downstream of PIK3R3 in liver cancer cells. Conclusion: PIK3R3 is upregulated in liver cancer and activates Akt signaling to control cancer growth by regulation of CDNK1C and SMC1A. Targeting PIK3R3 could be a promising treatment strategy for liver cancer that deserves further investigation. PIK3R3 is upregulated in liver cancer and activates Akt signaling to control cancer growth by regulation of CDNK1C and SMC1A.Targeting PIK3R3 could be a promising treatment strategy for liver cancer that deserves further investigation. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a common disease with a significant mortality, and there is no effective treatment for advanced patients. Growing evidence indicates that circRNAs are closely related to HCC progression, may be used as biomarkers and targets for the diagnosis and treatment of HCC. Recent researches have shown that circPUM1 may play an oncogene role in a variety of human cancers, but its role in HCC development has not been reported. Our study found that circPUM1 could promote the proliferation, migration and invasion of HCC cells in vitro. In addition, in vivo studies showed that circPUM1 could increase the development of HCC tumours and regulate the expression of EMT‐related proteins. Furthermore, we demonstrated that circPUM1 could promote the development of HCC by up‐regulating the expression of MAP3K2 via sponging miR‐1208. Our study suggested that circPUM1 may be a potential therapeutic target for HCC. [ABSTRACT FROM AUTHOR]