ABSTRACT
Our current study aimed to investigate the role and mechanism of circVIRMA in cervical cancer (CC) progression. CircVIRMA, microRNA-452-5p (miR-452-5p) and CREB3 regulatory factor (CREBRF) mRNA levels were examined in CC via quantitative real-time PCR (qRT-PCR). The protein level of CREBRF in CC was checked by Western blot. Cell Counting Kit-8 (CCK-8), colony formation, 5-Ethynyl-2'-deoxyuridine (EdU) staining, cell cycle, flow cytometry and transwell assays were conducted to estimate the effects of circVIRMA on malignant phenotypes of CC tumors. Western blot was used to measure related marker protein levels. The interaction between miR-452-5p and circVIRMA or CREBRF was predicted by bioinformatics analysis and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. Xenograft assay was used to assess the effect of circVIRMA on tumor growth in vivo. Immunohistochemistry (IHC) assay was performed to detect Ki-67 expression in tissues of mice. CircVIRMA and CREBRF levels were upregulated, while miR-452-5p was downregulated in CC tissues and cells. CircVIRMA silencing restrained CC cell proliferation, migration and invasion whereas induced apoptosis in vitro. In addition circVIRMA knockdown markedly attenuated xenograft tumor growth in vivo. circVIRMA was an efficient molecular sponge for miR-452-5p, and negatively regulated miR-452-5p expression. circVIRMA regulated CREBRF expression to modulate CC progression via miR-452-5p. MiR-452-5p downregulation reversed the effects of circVIRMA knockdown on CC progression. MiR-452-5p directly targeted CREBRF, and CREBRF overexpression partly restored the impact of miR-452-5p mimics on CC progression. circVIRMA mediated CC progression via regulating miR-452-5p/CREBRF axis, providing a novel therapeutic target for CC treatment.
ABSTRACT
BACKGROUND: Cancer patients have a higher risk of depression and are associated with severe adverse prognosis. The relationship between leisure-time physical activity (LTPA) and depressive symptoms in cancer patients is currently unclear. Therefore, our study mainly explores the potential association between LTPA and the weekly cumulative time of LTPA with depressive symptoms in cancer patients. METHODS: We included and analyzed 3368 cancer patients (aged >20 years) from the National Health and Nutrition Examination Survey (NHANES) of the United States from 1999 to 2018. The LTPA score was evaluated through a self-report questionnaire, while depressive symptoms were evaluated through the Health Questionnaire-9 (PHQ-9). Multiple logistic regression analysis was used to explore the relationship between LTPA duration and the occurrence of cancer-related depressiive symptoms. Linear correlation was studied using the restricted cubic spline method. RESULTS: According to a fully adjusted multivariate logistic regression model with confounding variables, the odds ratio (OR) between LTPA and depressive symptoms in cancer patients in this study was 0.59 (95 % confidence interval = 0.39, 0.92; P = 0.02). When the LTPA level was ≥300 min/week, the incidence of depressive symptoms was reduced by 59 % (OR = 0.41, 95 % CI = 0.21, 0.83). In addition, the cubic spline method was used to obtain a linear negative correlation between LTPA duration and tumor depressive symptoms. CONCLUSION: LTPA was negatively correlated with cancer-related depressive symptoms, and the cumulative time of LTPA/week was linearly correlated with depressive symptoms. The slope of the benefit curve changed significantly when the cumulative time of LTPA reached 600 min per week, suggesting that appropriately increasing LTPA had significant benefits on mental health of cancer patients.
