Exploring PANoptosis in breast cancer based on scRNA-seq and bulk-seq.

Background: PANoptosis, a cell death pathway involving pyroptosis, apoptosis, and necroptosis, is pivotal in the development of malignancy. However, in the field of breast cancer, the interaction between PANoptosis and tumor cells has not been thoroughly explored. Methods: We downloaded breast cancer data and GSE176078 single-cell sequencing dataset from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases to obtain PANoptosis-associated genes. To construct prognostic models, COX and LASSO regression was used to identify PANoptosis-associated genes with prognostic value. Finally, immune infiltration analysis and differential analysis of biological functions were performed. Results: Risk grouping was performed according to the prognostic model constructed by COX regression and LASSO regression. The low-risk group showed a better prognosis (P < 0.05) and possessed higher levels of immune infiltration and expression of immune checkpoint-related genes. In addition, the lower the risk score, the higher the degree of microsatellite instability (MSI). Meanwhile, radixin (RDX), the gene with the highest hazard ratio (HR) value among PANoptosis prognosis-related genes, was explicitly expressed in artery Iendothelial cells (ECs) and was widely involved in signaling pathways such as immune response and cell proliferation, possessing rich biological functions. Conclusion: We demonstrated the potential of PANoptosis-based molecular clustering and prognostic features in predicting the survival of breast cancer patients. Furthermore, this study has led to a deeper understanding of the role of PANoptosis in breast cancer and has the potential to provide new directions for immunotherapy of breast cancer.

miRNA-708 functions as a tumour suppressor in hepatocellular carcinoma by targeting SMAD3.

Hepatocellular carcinoma (HCC) is the most frequent subtype of primary liver cancer and the third most common cause of cancer-associated mortality worldwide. Previous studies have reported that microRNAs (miRNAs) serve key roles in the carcinogenesis and progression of HCC by regulating gene expression. The present study investigated the expression patterns, biological roles and underlying mechanisms of miRNA-708 (miR-708) in HCC. The expression levels of miR-708 in HCC tissue samples and cell lines were examined. Cell proliferation, migration and invasion assays were used to evaluate the effect of miR-708 on HCC cells. In addition, bioinformatic and western blotting analyses, and dual luciferase reporter assays were performed to investigate the direct gene target of miR-708. The results of the present study demonstrated that miR-708 expression was significantly decreased in HCC tissue samples and cell lines. In addition, the expression level of miR-708 was associated with increased HCC tumour stage. Furthermore, ectopic expression of miR-708 suppressed HCC cell proliferation, migration and invasion. The results of the present study also indicated that miR-708 targets SMAD family member 3 directly in vitro. The results of the present study indicated that miR-708 may be a novel target for future HCC therapy.

α-Mangostin suppresses lipopolysaccharide-induced invasion by inhibiting matrix metalloproteinase-2/9 and increasing E-cadherin expression through extracellular signal-regulated kinase signaling in pancreatic cancer cells.

Invasion and metastasis are major factors in the poor prognosis of pancreatic cancer, which remains one of the most aggressive and lethal diseases worldwide. α-mangostin, a major xanthone compound identified in the pericarp of mangosteen (Garcinia mangostana, Linn; GML), possesses unique biological activities, including antioxidant, antitumor and anti-inflammatory effects. Whether α-mangostin is able to inhibit the invasive ability of pancreatic cancer cells has not been elucidated. In the present study, α-mangostin was shown to inhibit the invasive ability of the pancreatic cancer cell lines MIAPaCa-2 and BxPC-3. The results showed that α-mangostin inhibited the growth of the pancreatic cancer cells in a dose- and time-dependent manner. At concentrations of <5 µM, α-mangostin had no significant effects on cytotoxicity, but significantly inhibited the invasion and migration of pancreatic cancer cells and the expression of matrix metalloproteinase (MMP)-2 and MMP-9, while increasing the expression of E-cadherin. The present data also showed that α-mangostin exerted an inhibitory effect on the phosphorylation of extracellular-signal-regulated kinase (ERK). Furthermore, the reduction of ERK phosphorylation by small interfering RNA (siRNA) potentiated the effect of α-mangostin. Taken together, the data suggest that α-mangostin inhibited the invasion and metastasis of pancreatic cancer cells by reducing MMP-2 and MMP-9 expression, increasing E-cadherin expression and suppressing the ERK signaling pathway. The present study suggests that α-mangostin may be a promising agent against pancreatic cancer.