Pancreatic adenosquamous carcinoma (ASPC) is a rare subtype of pancreatic cancer with lethal malignancy, and few studies have focused on the heterogeneity of ASPC. Here, we performed a single-cell sequencing procedure on pancreatic tumor tissue from an ASPC patient and a patient with high-grade intraductal papillary mucinous neoplasm (IPMN). Through the combined analysis of single-cell sequencing data from five pancreatic ductal adenocarcinoma (PDAC) patients, one IPMN patient, and one ASPC patient in a public database, we identified 11 main types of cells, including macrophages, B cells, cancer stem cells, ductal cells, fibroblasts, endo/stellate cells, neutrophils, acinar cells, T cells, natural killer (NK) cells, dendritic cells, and mast cells. Then, the different characteristics and differentiation paths of the immune microenvironment among IPMN, ASPC, and PDAC in macrophages, T cells, and cancer-associated fibroblasts (CAFs) were identified through multiple bioinformatics analyses. Two novel special cancer-associated fibroblasts were identified as nCAFs and imCAFs. Then, cancer cells in duct cells were identified using the infercnv software. Two ASPC-specific subgroups of cancer cells with squamous cell features were identified. Finally, the identified specific CAFs and cancer cells were mapped to TCGA-PAAD cohort through the cibersoftx software. All of these identified subgroups were calculated to have a significant prognostic value in pancreatic cancer patients. These findings will promote the clinical application of single-cell sequencing data of pancreatic cancer and deepen our understanding of ASPC.
Autophagy plays a key role in protecting cells against injury caused by foreign substances and maintaining the stability of cells. Nanomaterials easily cause cell autophagy, as foreign substances. In this experiment, we explored whether overexpressing miR-24 protects autophagy response of pancreatic cancer mediated by silica nanoparticles. Silica nanoparticles were first characterized and then used to treat pancreatic cancer cells in a co-culture system. Pancreatic cancer cells were divided into blank group (no transfection), miR-24 group (miR-24 mimics transfection), and control group (miR-24 inhibitors transfection). Immunohistochemistry (IHC) and immunoblots were used to monitor the expression of autophagy gene Beclin-1 and LC3-II. Transmission electron microscopy (TEM) was used to observe the formation of autophagosomes. The diameters of silica nanoparticles were about 100 nm before and after modification, with uniform size, high dispersion, and a negative potential state. The silica nanoparticles caused fluorescence aggregation in many pancreatic cancer cells, significantly increasing the LC3-I and LC3-II, and promoted the cytoprotective autophagy ability of pancreatic cancer cells. Transfection of miR-24 significantly inhibited Beclin-1 and LC3-II. Western blots also confirmed that the miR-24 significantly suppressed Beclin-1 and LC3-II. TEM results suggested that the miR-24 transfection significantly inhibited the release of autophagosomes. Silica nanomaterials can cause the protective autophagy response of pancreatic cancer cells and increase LC3-I and LC3-II. miR-24 can significantly inhibit the protective autophagy of pancreatic cancer cells caused by silica nanoparticles and suppressed Beclin-1 and LC3-II. miR-24 can also inhibited the release of autophagosomes in pancreatic cancer cells to inhibit the protective autophagy.
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