The purpose of this study was to determine the expression of miR-127 and analyze its prognostic and biological significance in breast cancer (BC). A quantitative reverse transcription PCR assay was performed to detect the expression of miR-127 in 15 pairs of BC and corresponding noncancerous tissues. The expression of miR-127 was detected in another 110 BC tissues and its correlations with clinicopathological factors of patients were examined. Univariate and multivariate analyses were performed to analyze the prognostic significance of miR-127 expression. The effects of miR-127 expression on malignant phenotypes of BC cells and its possible molecular mechanisms were further determined. miR-127 was significantly downregulated in BC tissues, and low miR-127 expression was significantly correlated with lymph node metastasis and advanced clinical stage. Patients with low miR-127 showed poorer overall survival than those with high miR-127. Multivariate analyses indicated that status of miR-127 was an independent prognostic factor for patients. Functional analyses showed that upregulation of miR-127 significantly inhibited growth, enhanced apoptosis, and reduced migration and invasion in BC cells by targeting the protooncogene BCL-6. Therefore, miR-127 may be a potential biomarker for predicting the survival of BC patients and might be a molecular target for treatment of human BCs.

Endoplasmic reticulum stress (ER stress) in intestinal epithelial cells (IECs) plays an important role in the pathogenesis and perpetuation of inflammatory bowel disease (IBD). The aim of this study is to explore the potential of berberine (BBR) in regulating pro-inflammatory cytokine-induced ER stress and apoptosis in IECs. ER stress in cultured Caco-2 cells was induced by IFN-γ/TNF-α and tunicamycin, respectively. The experimental groups were pretreated with BBR. Cell viability was determined by MTT assay. In vitro apoptosis was examined by flow cytometry using annexin V-FITC labeling. The molecular markers of ER stress, including GRP-78, p-JNK, caspase-12, and cleaved caspase-3 were analyzed by Western blot. Xbp-1 mRNA splicing was detected by RT-PCR. Pretreatment of BBR helped to survive in cytokine-induced Caco-2 cells. BBR significantly attenuated cytokine-induced Caco-2 apoptosis. GRP78 expression and xbp-1 mRNA splicing were enhanced significantly in the presence of IFN-γ/TNF-α and tunicamycin, and they could be dampened by BBR. Further study revealed BBR could downregulate JNK phosphorylation, and the level of caspase-12 and cleaved caspase-3. Berberine can ameliorate pro-inflammatory cytokines induced ER stress in vitro, and it might be one of the targeted therapeutic agents for IBD.

Background Undifferentiated carcinoma with osteoclast-like giant cells (OGCs) of pancreas (UCOGCP) is a rare subtype of pancreatic ductal adenocarcinoma (PDAC), which had poorly described histopathological and clinical features. Methods In this study, single-cell RNA sequencing (scRNA-seq) was used to profile the distinct tumor microenvironment of UCOGCP using samples obtained from one UCOGCP patient and three PDAC patients. Bioinformatic analysis was carried out and immunohistochemical (IHC) staining was used to support the findings of bioinformatic analysis. After quality control of the raw data, a total of 18,376 cells were obtained from these four samples for subsequent analysis. These cells were divided into ten main cell types following the Seurat analysis pipeline. Among them, the UCOGCP sample displayed distinct distribution patterns from the rest samples in the epithelial cell, myeloid cell, fibroblast, and endothelial cell clusters. Further analysis supported that the OGCs were generated from stem-cell-like mesenchymal epithelial cells (SMECs). Results Functional analysis showed that the OGCs cluster was enriched in antigen presentation, immune response, and stem cell differentiation. Gene markers such as LOX, SPERINE1, CD44, and TGFBI were highly expressed in this SMECs cluster which signified poor prognosis. Interestingly, in myeloid cell, fibroblasts, and endothelial cell clusters, UCOGCP contained higher percentage of these cells and unique subclusters, compared with the rest of PDAC samples. Conclusions Analysis of cell communication depicted that CD74 plays important roles in the formation of the microenvironment of UCOGCP. Our findings illustrated the genesis and function of OGCs, and the tumor microenvironment (TME) of UCOGCP, providing insights for prognosis and treatment strategy for this rare type of pancreatic cancer.