Integrating single-cell RNA-seq and spatial transcriptomics reveals MDK-NCL dependent immunosuppressive environment in endometrial carcinoma.

Objectives: The tumor microenvironment (TME) play important roles in progression of endometrial carcinoma (EC). We aimed to assess the cell populations in TME of EC. Methods: We downloaded datasets of single-cell RNA-seq (scRNA-seq) and spatial transcriptome (ST) for EC from GEO, and downloaded RNA-Seq (FPKM) and clinical data of TCGA-UCEC project from TCGA. The datasets were analyzed using R software. Results: We obtained 5 datasets of scRNA-seq, 1 of ST and 569 samples of RNA-seq. Totally, 0.2 billion transcripts and 33,408 genes were detected in 33,162 cells from scRNA-seq. The cells were classified into 9 clusters, and EC cells were originated from epithelial cells and ciliated cells. Gene set variation analysis (GSVA) indicated that the pathways enriched in the subclusters of epithelial cells and endothelial cells were significantly different, indicating great heterogeneity in EC. Cell-cell communication analyses showed that EC cells emitted the strongest signals, and endothelial cells received more signals than other cells. Further analysis found that subclusters of 1 and 2 of epithelial cells were showed a more malignant phenotype, which may confer malignant phenotype to subcluster of 0 of endothelial cells through MK pathway by MDL-NCL signal. We also analyzed communications between spatial neighbors with ST data and confirmed the findings on MDL-NCL in cell-cell communication. TCGA and GEO analyses indicated that the expression levels of NCL was inversely correlated with ImmuneScore. Conclusion: Our study revealed EC cells can confer malignant phenotype to endothelial cells by MDK-NCL signal, and NCL is associated with suppressed immune activity. EC cells may shape TME by inhibiting immune cells and "educating" stromal cells via MDK-NCL signal.

Esomeprazole overcomes paclitaxel-resistance and enhances anticancer effects of paclitaxel by inducing autophagy in A549/Taxol cells.

Non-small-cell lung cancer (NSCLC) is one of the most common malignancies, and the occurrence of drug-resistance severely limits the efficacy of anticancer drugs in the treatment of NSCLC. Identification of new agents to reverse drug-resistance in NSCLC treatment is of great importance and urgency both clinically and scientifically. In the present study, we found that A549/Taxol cells displayed a high level of resistance to paclitaxel with the resistance index up to 231. Importantly, esomeprazole could potentiate the antiproliferative effect of paclitaxel in A549/Taxol cells, but not in A549 cells. Further exploration on the underlying mechanisms revealed that esomeprazole decreased the intracellular pH via inhibiting V-ATPase expression in A549/Taxol cells. Meanwhile, esomeprazole pretreatment significantly promoted paclitaxel-induced polymerization of tubulin and enhanced the proportion of G2/M-arrested cells in A549/Taxol cells. Unfortunately, esomeprazole could only result in a slight decrease in the expression of P-gp in A549/Taxol cells. Interestingly, esomeprazole significantly increased paclitaxel-induced apoptosis, which was impeded by the autophagy inhibitor 3-MA in A549/Taxol cells. Taken together, our data suggest that esomeprazole is a promising chemosensitizer against paclitaxel-resistant NSCLC by inducing autophagy. Our study also offers a new strategy to solve the paclitaxel-resistance problem during NSCLC treatment.

MicroRNA-100 suppresses human gastric cancer cell proliferation by targeting CXCR7.

microRNAs (miRs) are a class of small non-coding RNAs that have been demonstrated to have a crucial role in tumorigenesis of human cancers, including gastric cancer (GC). Previous results have established that miR-100 participated in the development of GC; however, the underlying mechanism remains largely unknown. The preesent study utilized reverse transcription-quantitative polymerase chain reaction to analyze the expression of miR-100 in GC tissues and adjacent normal tissues. The present results indicated that the expression of miR-100 was downregulated in GC tissues when compared to the adjacent normal tissues. Furthermore, low miR-100 expression was observed to be associated with lymph node metastasis, tumor diameter and tumor stage. In addition, Kaplan-Meier analysis revealed that patients with low miR-100 expression tended to have a shorter overall survival. The miR-100 was further identified as an independent prognostic factor for overall survival. Notably, the levels of chemokine (CXC motif) receptor 7 (CXCR7) were inversely correlated with miR-100 in GC cell lines. Furthermore, miR-100 overexpression or CXCR7 depletion decreased in vitro GC cell proliferation. Bioinformatics analysis indicated that miR-100 may bind to the 3'-untranslated region of CXCR7 to prevent the initiation of protein translation. Thus, miR-100 may function as a tumor suppressor in GC, partly by regulating the expression of CXCR7, and the regulation of miR-100 expression may be a potential strategy for the treatment of GC patients.