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There is growing evidence on the clinical significance of Tumor Microenvironment (TME) cells in predicting prognosis and therapeutic effects. However, cell interactionsin tumor microenvironments have not been thoroughly studied or systematicallyanalyzed so far. In this study, 22 immune cell components in the lung adenocarcinoma(LUAD) TME were analyzed using gene expression profile from The Cancer GenomeAtlas (TCGA), Gene Expression Omnibus (GEO) . The TME based molecular subtypesof LUAD were defined to evaluate further the relationship between molecular subtypes,prognosis, and clinical characteristics. A TME risk score model was constructed byusing the differentially expressed genes (DEGs) of molecular subtypes. The relationshipbetween the TME score and clinical characteristics and genomic mutations wascompared to identify the genes that have significant associations with the TME. Thecomprehensive analysis of the TME characteristics maybe helpful in revealing theresponse of LUAD patients to immunotherapy, providing a new strategy forimmunotherapy.

[Background] Coix lacryma-jobi L. is a nourishing food and a traditional Chinese medicine and has been used for the treatment of neuralgia, inflammatory diseases, and rheumatism. Little is known about the anti-tumor of Coix lacryma-jobi L.. In this study, the cytotoxic effects of Coix lacryma-jobi L. on HeLa, HepG2, and SGC-7901 were evaluated.[Methods] The cytotoxic active compounds were isolated and extraction from the stems and leaves of Coix lacryma-jobi L. The structural identification of the compound was determined using ultraviolet spectroscopy, Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The cytotoxic activity in vitro effect of the compound was determined using CCK-8, Flow cytometry, and DNA Topo I inhibition experiments.[Results] A compound F2 was isolated and purified from the petroleum ether extract of Coix lacryma-jobi L. stems and leaves. It was identified as the cycloartenol. The minimum IC50 values of HeLa, HepG2 and SGC-7901 cells for this compound were 500, 537.7, and 336.8 μg/mL, respectively. The compound had pro-apoptotic effects on three types of tumor cells, and had a significant inhibitory effect on DNA topoisomerase I.[Conclusion] This study demonstrates that cycloartenol has good cytotoxic activity in vitro, suggesting that cycloartenol could be a potential candidate as a natural antitumor drug.

As a potential oncogene, nucleolar and spindle-associated protein 1 (NUSAP1) is involved in the regulation of tumor cell proliferation, metastasis and drug resistance. However, the role of NUSAP1 in non-small cell lung cancer (NSCLC) remains unclear. The present study aimed to investigate the biological function and underlying molecular mechanisms of NUSAP1 in NSCLC. NUSAP1 expression was measured in NSCLC tissues and cell lines via immunohistochemistry and western blotting, respectively. NSCLC cell lines stably inhibiting NUSAP1 were established to investigate its effects on cell proliferation, colony formation and invasion, and on in vivo tumorigenicity. Additionally, the upstream and downstream mechanisms of NUSAP1 in regulating NSCLC progression were investigated. The results indicated that NUSAP1 expression was upregulated in NSCLC tissues and cell lines. High NUSAP1 expression was associated with tumor size, TNM stage, lymph node metastasis and poor patient survival, whereas knockdown of NUSAP1 inhibited NSCLC cell proliferation, colony formation and invasion. Furthermore, downregulation of NUSAP1 decreased the growth of NSCLC xenografts in vivo . In addition, myocyte enhancer factor 2D (MEF2D) directly targeted the NUSAP1 promoter, thereby enhancing the mRNA and protein expression levels of NUSAP1. Moreover, the results demonstrated that MEF2D expression was upregulated in NSCLC tissues and was positively correlated with NUSAP1 expression. MEF2D-knockdown decreased NSCLC cell proliferation, colony formation and invasion. NUSAP1 upregulation reversed the effects of MEF2D-knockdown on NSCLC progression. Furthermore, it was observed that MEF2D-knockdown inhibited the accumulation and nuclear translocation of β-catenin, thereby repressing the activation of the Wnt/β-catenin signaling pathway in NSCLC cells, whereas NUSAP1 upregulation rescued the effects of MEF2D-knockdown on the activation of the Wnt/β-catenin signaling pathway. In conclusion, the findings of the present study indicated that the MEF2D/NUSAP1 signaling pathway promoted NSCLC progression by inducing the activation of Wnt/β-catenin signaling, and this novel mechanism may represent a potential treatment target for patients with NSCLC.

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