Screening and verification of hub genes in esophageal squamous cell carcinoma by integrated analysis.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors. However, the mechanisms underlying ESCC tumorigenesis have not been fully elucidated. Thus, we aimed to determine the key genes involved in ESCC tumorigenesis. The following bioinformatics analyses were performed: identification of differentially expressed genes (DEGs); gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis; integrated analysis of the protein-protein interaction network and Gene Expression Profiling Interactive Analysis database for validation of hub genes. Finally, western blotting and qPCR were used to explore the expression of cell division cycle 6 (CDC6) in ESCC cell lines. Immunohistochemistry analysis of ESCC samples from patients and matched clinical characteristics was used to determine the effects of CDC6. A total of 494 DEGs were identified, and functional enrichment was mainly focused on cell cycle and DNA replication. Biological pathway analysis of the hub genes was closely related to the cell cycle. We found that CDC6 was upregulated in ESCC cell lines and patient tissues and was related to the clinicopathological characteristics of ESCC. In conclusion, this study identified hub genes and crucial biological pathways related to ESCC tumorigenesis and integrated analyses indicated that CDC6 may be a novel diagnostic and therapeutic target for ESCC.

The association of pre-cancer diagnosis cardiovascular risk factors with memory aging after a cancer diagnosis, overall and by race/ethnicity.

PURPOSE: Cardiovascular risk factors (CVRFs) are associated with increased risk for cognitive impairment and decline in the general population, but less is known about how CVRFs might influence cognitive aging among older cancer survivors. We aimed to determine how CVRFs prior to a cancer diagnosis affect post-cancer diagnosis memory aging, compared to cancer-free adults, and by race/ethnicity. METHODS: Incident cancer diagnoses and memory (immediate and delayed recall) were assessed biennially in the US Health and Retirement Study (N = 5,736, 1998-2018). CVRFs measured at the wave prior to a cancer diagnosis included self-reported cigarette smoking, obesity, diabetes, heart disease, hypertension, and stroke. Multivariable-adjusted linear mixed-effects models evaluated the rate of change in standardized memory score (SD/decade) post-cancer diagnosis for those with no, medium, and high CVRFs, compared to matched cancer-free adults, overall and stratified by sex and race/ethnicity. RESULTS: Higher number of CVRFs was associated with worse baseline memory for both men and women, regardless of cancer status. Cancer survivors with medium CVRFs had slightly slower rates of memory decline over time relative to cancer-free participants (0.04 SD units/decade [95% CI: 0.001, 0.08]). Non-Hispanic Black (NHB) and Hispanic cancer-free participants and cancer survivors had worse baseline memory than their Non-Hispanic White (NHW) counterparts. CONCLUSIONS: CVRFs were associated with worse baseline memory function, but not decline, for cancer-free adults and cancer survivors. Racial disparities were largely similar between cancer survivors and cancer-free adults. IMPLICATIONS FOR CANCER SURVIVORS: These findings may inform hypotheses about pre-diagnosis multimorbidity and cognitive aging of cancer survivors from diverse groups.

Paeoniflorin regulates RhoA/ROCK1 and Nrf2 pathways in PDLIM1-dependent or independent manners in oxidative stressed melanocytes.

BACKGROUND: The adhesive properties of vitiligo melanocytes have decreased under oxidative stress., cytoskeleton proteins can control cell adhesion. Paeoniflorin (PF) was proved to resist hydrogen peroxide (H2O2)-induced oxidative stress in melanocytes via nuclear factorE2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. OBJECTIVES: This study was to investigate whether PF exerts anti-oxidative effect through influencing cytoskeleton markers or potential signaling pathway. METHODS: Human Oxidative Stress Plus array was used to identify the differentially expressed genes between H2O2 + PF group and H2O2 only group, in PIG1 and PIG3V melanocyte cell lines respectively. Western blotting was used to verify the PCR array results and to test the protein expression levels of cytoskeleton markers including Ras homolog family member A (RhoA), Rho-associated kinase 1 (ROCK1) and antioxidative marker Nrf2. Small interfering RNA was used to knock down PDZ and LIM domain 1 (PDLIM1). RESULTS: PF increased the expressions of PDLIM1, RhoA and ROCK1 in H2O2-induced PIG1, in contrast, decreased the expressions of PDLIM1 and ROCK1 in H2O2-induced PIG3V. Knockdown of PDLIM1 increased the expressions of RhoA and Nrf2 in PF-pretreated H2O2-induced PIG1, and ROCK1 and Nrf2 in PF-pretreated H2O2-induced PIG3V. CONCLUSIONS: PF regulates RhoA/ROCK1 and Nrf2 pathways in PDLIM1-dependent or independent manners in H2O2-induced melanocytes. In PIG1, PF promotes PDLIM1 to inhibit RhoA/ROCK1 pathway or activates Nrf2/HO-1 pathway, separately. In PIG3V, PF directly downregulates ROCK1 in PDLIM1-independent manner or upregulates Nrf2 dependent of PDLIM1.