Analytical Cellular Pathology (Amsterdam)最新文献

Objective: This study is aimed at exploring the association between autophagy and tumor immune infiltration (TII) in colorectal cancer (CRC).

Methods and materials: We downloaded the transcriptome profiling and clinical data for CRC from The Cancer Genome Atlas (TCGA) database and obtained the normal colon transcriptome profiling data from Genotype-Tissue Expression Project (GTEx) database. The list of autophagy-related signatures was obtained from the Human Autophagy Database. We isolated the autophagy-related genes from the CRC gene expression matrix and constructed an autophagy-related prognostic (ARP) risk model. Then, we constructed a multiROC curve to validate the prognostic ability of the ARP risk model. CIBERSORT was used to determine the fractions of 22 immune cells in each CRC sample, and the association between these TII cells and CRC clinical variables was further investigated. Finally, we estimated the association of 3 hub-ARP signatures and 20 different types of TII cell distribution.

Results: We classified 447 CRC patients into 224 low-risk and 223 high-risk patients using the median ARP risk score. According to the univariate survival test results, except for gender (P = 0.672), age (P = 0.008), cancer stage, and pathological stage T, M, and N were closely correlated with the prognosis of CRC patients (P < 0.001). Multivariate survival analysis results indicate that age and rescore were the only independent prognostic indicators with significant differences (P < 0.05). After merging the immune cell distribution (by CIBERSORT) with the CRC clinical data, the results indicate that activated macrophage M0 cells exhibited the highest clinical response, which included cancer stage and stage T, N, and M. Additionally, six immune cells were closely associated with cancer stage, including regulatory T cells (Tregs), gamma delta T cells, follicular helper T cells, activated memory CD4 T cells, activated NK cells, and resting dendritic cells. Finally, we evaluated the correlation of ARP signatures with TII cell distribution. Compared with the other correlation, NRG1 and plasma cells (↑), risk score and macrophage M1 (↑), NRG1 and dendritic cell activated (↑), CDKN2A and T cell CD4 memory resting (↓), risk score and T cell CD8 (↑), risk score and T cell CD4 memory resting (↓), and DAPK1 and T cell CD4 memory activated (↓) exhibited a stronger association (P < 0.0001).

Conclusions: In summary, we explored the correlation between the risk of autophagy and the TII microenvironment in CRC patients. Furthermore, we integrated different CAR signatures with tumor-infiltrating immune cells and found robust associations between different levels of CAR signature expression and immune cell infiltrating density.

Alzheimer's disease (AD) is one common degenerative disorder. However, the effects of miR-590-5p on AD and the mechanism on modulation of AD development were unclear. In this study, the miR-590-5p level in AD patients at mild, moderate, and severe stage as well as APP/PS1 transgenic mice was detected by qRT-PCR. The relationship of miR-590-5p and pellino-1 (PELI1) was identified by double luciferase reporter gene assay. Afterwards, both BV-2 and HT22 cells were exposed to β-amyloid (Aβ) peptides to mimic AD cell model. Then, the roles of miR-590-5p upregulation or PELI1 silence in cell proliferation and apoptosis were explored by CCK-8 assay and TUNEL assay, and the expression of apoptosis-related proteins was detected by western blotting. Furthermore, the involvements of the downstream Traf3/MAPK P38 pathway with the roles of miR-590-5p in AD were measured by western blotting. Our results showed that knockdown of miR-590-5p was found in AD patients, mice model, and Aβ-induced cell model. Notably, PELI1 was proved as a target gene of miR-590-5p. miR-590-5p mimic or PELI1 silence significantly promoted cell proliferation and inhibited cell apoptosis, as well as suppressed the activation of Traf3/MAPK P38 pathway both in Aβ-induced BV-2 and HT22 cells. The effects of PELI1 overexpression on cell proliferation, apoptosis, and Traf3/MAPK P38 pathway were partly abrogated by miR-590-5p mimic both in BV-2 and HT22 cells. In conclusion, miR-590-5p was expressed at lower levels in AD, and miR-590-5p/PELI1 axis might be involved in the progression of AD by the downstream Traf3/MAPK P38 pathway.

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents with poor prognosis. MicroRNA-181a-5p (miR-181a-5p) is involved in the progression of various tumors; however, its role and underlying mechanism in osteosarcoma remains unclear. In this study, we found that miR-181a-5p was upregulated in human osteosarcoma cells and tissues. miR-181a-5p mimic significantly promoted, while miR-181a-5p inhibitor blocked the proliferation, colony formation, migration, invasion, and cell cycle progression of osteosarcoma cells. Mechanistically, miR-181a-5p bound to the 3'-untranslational region of phosphatase and tensin homolog (PTEN) and reduced its protein expression, thereby activating protein kinase B (PKB/AKT) pathway. Either PTEN overexpression or AKT inhibition notably blocked the tumor-promoting effects of miR-181a-5p. Moreover, we observed that miR-181a-5p mimic further inhibited growth of human osteosarcoma cells in the presence of adriamycin or cisplatin. Overall, miR-181a-5p promotes osteosarcoma progression via PTEN/AKT pathway and it is a promising therapeutic target to treat osteosarcoma.