Int J Med Sci
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Nucleus accumbens-associated protein 1 (NACC1) regulates various types of biological processes. It is a transcription factor associated with cancer. NACC1 is overexpressed in many human malignancies and can regulate the progression, metastasis, and drug resistance of cancer cells. ⋯ Concurrently, ADAM9 knockdown affected the activity of AML cells by decelerating the growth rate, promoting apoptosis, and blocking cell cycle progression. In addition, the AKT activator SC79 restored the inhibited cell proliferation after NACC1 knockdown and ADAM9 knockdown. In conclusion, our study suggested that the NACC1/ADAM9/PI3K/AKT axis is crucial for sustaining the survival of AML cells, indicating that NACC1 may be a viable target for treating AML.
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RAC1, a member of the Rho family GTPases, has been implicated in various cancers, yet its pan-cancer landscape and role in the tumor immune microenvironment remain underexplored. This study presents a comprehensive analysis of RAC1 across 33 cancer types, revealing its high expression in a broad range of cancers and its association with poor prognosis. RAC1 expression correlates with genomic alterations, including CNVs, TMB, and MSI. ⋯ Functional enrichment analysis showed that high RAC1 expression is linked to lower enrichment in B cell activation and immune response pathways. Single-cell transcriptome analysis identified RAC1 expression primarily in epithelial cells, associated with tumor progression, and spatial transcriptome analysis showed a mutually exclusive co-localization between B cell infiltration regions and RAC1-expressing epithelial cells. Based on RAC1 expression and B cell interaction, a prognostic signature was established to predict prognosis at the pan-cancer level.
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Diabetic retinopathy (DR) is a microvascular complication of diabetes characterized by an inflammatory response. The H19 gene plays a role in regulating inflammation and is associated with chronic systemic inflammation. This study aims to investigate the potential correlation between single-nucleotide polymorphisms (SNPs) in the H19 gene and the development of DR. ⋯ Additionally, diabetic individuals with the H19 SNP rs3741219 AG+GG genotype also showed significantly higher serum creatinine (p = 0.034), lower glomerular filtration rate (GFR) (p = 0.013), higher total cholesterol/HDL ratio (p = 0.031), and higher triglycerides (p = 0.012). In an age-based subgroup analysis, GFR was significantly lower in diabetic patients with an onset of diabetes before 45 years and with the H19 SNP rs3741219 AG+GG genotype (p = 0.012). In conclusion, the presence of the H19 SNP rs3741219 variant is associated with a higher risk of DR in individuals with early-onset diabetes, and the relationship between the rs3741219 variant and decreased GFR is particularly pronounced in this population.
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Background: The progression and metastasis of colorectal cancer (CRC) remain major clinical challenges due to a lack of effective therapeutic targets. Our preliminary study identified the upregulation of the propionyl-CoA carboxylase alpha chain (PCCA) gene in CRC, prompting further investigation into its functional roles. Methods: Bioinformatics analysis, colorectal tumor tissues, and CRC cell lines were used to determine PCCA expression. ⋯ Moreover, PCCA knockdown suppressed CRC tumor growth and lung metastasis, accompanied by an increase in M1-macrophage polarization. Conclusion: Knockdown PCCA inhibits the progression and metastasis of CRC, which is associated with EMT reversion, ERK/GSK3β signaling inactivation, and M1-macrophage polarization. These findings suggest that PCCA is a potential target for controlling CRC.
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Background: Doublecortin-like kinase 1 (DCLK1) has been revealed to be involved in modulating cancer stemness and tumor progression, but its role in prostate cancer (PCa) remains obscure. Castration-resistant and metastatic PCa exhibit aggressive behaviors, and current therapeutic approaches have shown limited beneficial effects on the overall survival rate of patients with advanced PCa. This study aimed to investigate the biological role and potential molecular mechanism of DCLK1 in the progression of PCa. ⋯ Consistent with the in vitro findings, the in vivo findings confirmed that DCLK1 promoted the tumorigenicity and stem cell-like traits of PCa cells via Hippo-YAP signaling. Conclusion: DCLK1 promotes stem cell-like characteristics by inducing LATS1-mediated YAP signaling activation, ultimately leading to PCa tumor growth and progression. Thus, our findings identify an attractive candidate for the development of cancer stem cell-targeted therapies to improve treatment outcomes in advanced PCa.