PKD3 promotes metastasis and growth of oral squamous cell carcinoma through positive feedback regulation with PD-L1 and activation of ERK-STAT1/3-EMT signalling

Oral squamous cell carcinoma(OSCC)has a high incidence of metastasis.Tumour immunotherapy targeting PD-L1 or PD-1 has been revolutionary;however,only a few patients with OSCC respond to this treatment.Therefore,it is essential to gain insights into the molecular mechanisms underlying the growth and metastasis of OSCC.In this study,we analysed the expression levels of protein kinase D3(PKD3)and PD-L1 and their correlation with the expression of mesenchymal and epithelial markers.We found that the expression of PKD3 and PD-L1 in OSCC cells and tissues was significantly increased,which correlated positively with that of mesenchymal markers but negatively with that of epithelial markers.Silencing PKD3 significantly inhibited the growth,metastasis and invasion of OSCC cells,while its overexpression promoted these processes.Our further analyses revealed that there was positive feedback regulation between PKD3 and PD-L1,which could drive EMT of OSCC cells via the ERK/STAT1/3 pathway,thereby promoting tumour growth and metastasis.Furthermore,silencing PKD3 significantly inhibited the expression of PD-L1,and lymph node metastasis of OSCC was investigated with a mouse footpad xenograft model.Thus,our findings provide a theoretical basis for targeting PKD3 as an alternative method to block EMT for regulating PD-L1 expression and inhibiting OSCC growth and metastasis.

基于转录组测序数据对Weissella confusa XU1中低聚木糖代谢系统的分析

【目的】近年来由于在发酵方面的良好特性,低聚木糖的益生作用越来越得到公众的关注。研究发现相比于葡萄糖和木糖WeissellaconfusaXU1在以低聚木糖为唯一碳源时生长情况最好。本文将对WeissellaconfusaXU1中低聚木糖的代谢机制进行研究。【方法】本研究分别以葡萄糖、木糖和低聚木糖作为唯一碳源对Weissella confusa XU1进行转录组测序并进行比较分析。【结果】通过转录组分析发现以低聚木糖为唯一碳源的处理中部分编码MFS转运蛋白和糖基水解酶的基因转录水平显著上升,WeissellaconfusaXU1中的糖酵解过程和磷酸戊糖途径也得到显著增强。【结论】本研究根据转录组数据分析得出Weissella confusa XU1中的低聚木糖代谢机制。本研究首次在革兰氏阳性菌中发现MFS转运蛋白参与到低聚木糖转运的过程,为提高微生物对木聚糖利用效率进行分子改造提供了改造方向,该机制为低聚木糖代谢的研究和Weissella的工业化应用提供了新的思路。