Circular RNAs (circRNAs) represent a class of endogenous noncoding RNAs that have recently been recognized as important regulators of gene expression and pathological networks. However, their transcriptional activities and functional mechanisms in cancer remain largely unknown. Here, we present results from a global circRNA expression and functional analysis of patients with hepatocellular carcinoma (HCC). Using a circRNA microarray, we identified 226 differentially expressed circRNAs, of which 189 were significantly upregulated and 37 were downregulated. High expression of circRNA_100338, one of the upregulated circRNAs in HCC, is closely correlated with a low cumulative survival rate and metastatic progression in HCC patients with hepatitis B. Furthermore, our in silico and experimental analyses identified miR-141-3p as a direct target of circRNA_100338. Thus, circRNA_100338 functions as an endogenous sponge for miR-141-3p in HCC. In addition, we identified the crucial antagonistic roles of circRNA_100338 and miR-141-3p in the regulation of invasive potential in liver cancer cells. Overall, the differential expression of multiple circRNAs in HCC tissues and their clinical significance in hepatitis B-related HCC patients as revealed by our study suggests that circRNA_100338 is a potentially valuable biomarker for HCC diagnosis and target for HCC therapeutics.
on behalf of the Hemangioma Investigator Group abstract BACKGROUND: There has been a dramatic increase in the off-label use of ophthalmic timolol maleate, a β-blocker used for infantile hemangioma (IH) treatment as a topical counterpart to oral propranolol. Its safety and efficacy in a pediatric population with IH have not been evaluated in a large cohort. Our goal was to retrospectively assess timolol's effectiveness, discern characteristics associated with response, and document reported adverse events.
Pyroptosis is a newly discovered programmed cell death that is associated with tumor progression, prognosis, and treatment response. However, the potential roles of pyroptosis-related genes (PRGs) in the tumor microenvironment (TME) remain unclear. We described the alterations of PRGs in 1109 colorectal cancer (CRC) samples from genetic and transcriptional fields and evaluated their expression patterns from four independent datasets. We identified two distinct molecular subtypes and found that multi-layer PRG alterations were correlated with patient clinicopathological features, prognosis, and TME cell-infiltrating characteristics. Then, a PRG_score for predicting recurrence-free survival (RFS) was constructed and its predictive capability in CRC patients was validated. Consequently, we constructed a highly accurate nomogram for improving the clinical applicability of the PRG_score. A low PRG_score, characterized by increased microsatellite instability-high (MSI-H), mutation burden, and immunity activation, indicated favorable odds of RFS. Moreover, the PRG_score was significantly associated with the cancer stem cell (CSC) index and chemotherapeutic drug sensitivity. Our comprehensive analysis of PRGs in CRC demonstrated their potential roles in the tumor-immune-stromal microenvironment, clinicopathological features, and prognosis. These findings may improve our understanding of PRGs in CRC and pave a new path for the assessment of prognosis and the development of more effective immunotherapy strategies.
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