Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy with a complex tumor ecosystem. How the interplay between tumor cells, EBV, and the microenvironment contributes to NPC progression and immune evasion remains unclear. Here we performed single-cell RNA sequencing on ~104,000 cells from 19 EBV + NPCs and 7 nonmalignant nasopharyngeal biopsies, simultaneously profiling the transcriptomes of malignant cells, EBV, stromal and immune cells. Overall, we identified global upregulation of interferon responses in the multicellular ecosystem of NPC. Notably, an epithelial-immune dual feature of malignant cells was discovered and associated with poor prognosis. Functional experiments revealed that tumor cells with this dual feature exhibited a higher capacity for tumorigenesis. Further characterization of the cellular components of the tumor microenvironment (TME) and their interactions with tumor cells revealed that the dual feature of tumor cells was positively correlated with the expression of co-inhibitory receptors on CD8 + tumor-infiltrating T cells. In addition, tumor cells with the dual feature were found to repress IFN-γ production by T cells, demonstrating their capacity for immune suppression. Our results provide new insights into the multicellular ecosystem of NPC and offer important clinical implications.
Interlayer friction between the atomic planes of 2D materials and heterostructures is a promising probe of the physics in their interlayer couplings and superlubricity. However, it is still challenging to measure the interlayer friction between well-defined 2D layers. We propose an approach of thermally assisted mechanical exfoliation and transfer to fabricate various 2D flake-wrapped atomic force microscopy (AFM) tips and to directly measure the interlayer friction between 2D flakes in single-crystalline contact. First, superlubricity between different 2D flakes and layered bulk materials is achieved with a friction coefficient as low as 10. The rotation angle dependence of superlubricity is observed for friction between graphite layers, whereas it is not observed between graphite and h-BN because of the incommensurate contact of the mismatched lattices. Second, the interlayer lateral force map between ReS layers is measured with atomic resolution, showing hexagonal patterns, as further verified by theoretical simulations. The tribological system constructed here offers an experimental platform to study interlayer couplings and friction between 2D flakes and layered bulk materials.
NRP1 as multifunctional non-tyrosine-kinase receptors play critical roles in tumor progression. MicroRNAs (miRNAs) are an important class of pervasive genes that are involved in a variety of biological functions, particularly cancer. It remains unclear whether miRNAs can regulate the expression of NRP1. The goal of this study was to identify miRNAs that could inhibit the growth, invasion and metastasis of gastric cancer by targeting NRP1 expression. We found that miR-338 expression was reduced in gastric cancer cell lines and in gastric cancer tissues. Moreover, we found that miR-338 inhibited gastric cancer cell migration, invasion, proliferation and promoted apoptosis by targeting NRP1 expression. As an upstream regulator of NRP1, miR-338 directly targets NRP1. The forced expression of miR-338 inhibited the phosphorylation of Erk1/2, P38 MAPK and Akt; however, the expression of phosphorylated Erk1/2, P38 MAPK and Akt was restored by the overexpression of NRP1. In AGS cells infected with miR-338 or transfected with SiNRP1, the protein levels of fibronectin, vimentin, N-cadherin and SNAIL were decreased, but the expression of E-cadherin was increased. The expression of mesenchymal markers in miR-338-expressing cells was restored to normal levels by the restoration of NRP1 expression. In vivo, miR-338 also decreased tumor growth and suppressed D-MVA by targeting NRP1. Therefore, we conclude that miR-338 acts as a novel tumor suppressor gene in gastric cancer. miR-338 can decrease migratory, invasive, proliferative and apoptotic behaviors, as well as gastric cancer EMT, by attenuating the expression of NRP1.
The 2011 outbreak in China showed that poliomyelitis-free countries remain at risk for outbreaks while the poliovirus circulates anywhere in the world. Global eradication of poliomyelitis will benefit all countries, even those that are currently free of poliomyelitis.
Within the family of RTKs (receptor tyrosine kinases), PDGFR (platelet-derived growth factor receptor) has been implicated in carcinogenesis and tumour development. miRNAs (microRNAs), which can target the mRNAs (messenger RNAs) of cancer-associated genes, are abnormally expressed in various cancers. In this study, our aim was to identify the miRNAs that target PDGFR-α/β and to study the functions of these miRNAs. miR-34a was predicted to target PDGFR, and luciferase reporter assays showed that miR-34a could directly target PDGFR. Meanwhile, we found that miR-34a was down-regulated in gastric cancer tissues and was associated with metastasis. Our findings showed that miR-34a could inhibit gastric cancer cell migration, invasion and proliferation, but these tumourigenic properties were only partially restored when PDGFR-α/β was overexpressed. In subsequent experiments, we found that the overexpression of both PDGFR and MET could completely restore the gastric cancer tumourigenic properties. Moreover, the cancer-associated cell signalling pathway was studied, and we found that miR-34a could inhibit Akt [PKB (protein kinase B)] phosphorylation, which was restored by the overexpression of both PDGFR and MET. In conclusion, miR-34a may act as a potential tumour suppressor in gastric cancer and is associated with the mechanisms of gastric cancer metastasis; miR-34a can inhibit gastric cancer tumourigenesis by targeting PDGFR and MET through the PI3K (phosphoinositide 3-kinase)/Akt pathway.
CarNAC4 is a typical stress-responsive NAC transcription factor and enhances drought and salt stress tolerances in transgenic Arabidopsis. Chickpea (Cicer arietinum L.) is relatively vulnerable to abiotic stress conditions, but the tolerance mechanisms for such stresses in chickpea are largely unknown. To identify stress-related factors in chickpea, we previously constructed a cDNA library of chickpea leaves exposed to drought stress conditions. A cDNA encoding a putative NAC transcription factor (CarNAC4) was identified as a putative stress-responsive gene. Our study indicated that the transcript levels of CarNAC4 were enhanced in response to several abiotic stresses and phytohormones. Promoter analysis demonstrated that multiple stress-related cis-acting elements exist in promoter region of CarNAC4. CarNAC4 is localized in the nucleus and binds to the DNA sequence containing CGT[G/A], while the C-terminal region of CarNAC4 contains a transcriptional activation domain. Over-expression of CarNAC4 in Arabidopsis plants improved tolerance to drought and salt stresses. Transgenic plants exhibited greater reduced rates of water loss and more proline accumulation than Col-0 plants under drought stress and less MDA contents than Col-0 plants under salt stress. In addition, over-expression of CarNAC4 enhanced the expression of stress-responsive genes such as RD29A, ERD10, COR15A, COR47, KIN1 and DREB2A. These results indicated that CarNAC4 functions as a transcription factor involved in the regulation of drought and salt stress response.
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