趋化因子CXCL2通过上调肾癌细胞lnc-ARRDC3-1促进EMT的机制研究

lncRNAs在肿瘤中起着致癌或抑癌作用；肿瘤相关巨噬细胞（TAMs）在肾癌中浸润增加，可通过分泌趋化因子CXCL2等调控lncRNAs的表达，在肿瘤侵袭转移中发挥促进或抑制作用。我们利用芯片技术发现：lnc-ARRDC3-1与趋化因子CXCL2在肾癌中高表达；生物信息学分析表明：lnc-ARRDC3-1与CXCL2mRNA水平呈正相关；体外实验发现：重组人CXCL2可上调肾癌细胞lnc-ARRDC3-1的表达；沉默lnc-ARRDC3-1可抑制肾癌细胞增殖、侵袭能力及上皮-间质转化（EMT）。由此，我们提出肾癌进展的新机制：TAMs分泌的趋化因子CXCL2通过上调肾癌细胞lnc-ARRDC3-1表达，促进肾癌细胞EMT，导致肾癌侵袭和转移。本项目拟阐明CXCL2上调肾癌细胞lnc-ARRDC3-1表达，进而促进肾癌细胞EMT的分子机制，有望揭示肾癌转移的新机制，为肾癌靶向治疗提供新靶点。

Recent studies have shown that long non-coding RNAs (lncRNAs) act as oncogenes or tumor suppressor genes in human cancer. Tumor associated macrophages (TAMs) infiltrate through renal cell carcinoma tissues and play important roles in tumor progression and metastasis by secreting chemokines and regulating the expression of lncRNAs. Gene Expression Microarray has revealed that lnc-ARRDC3-1 and CXCL2 mRNA are overexpressed in renal cell carcinoma, and we found that the expression of lnc-ARRDC3-1 correlates positively with CXCL2 mRNA using bioinformatics analysis. Further study suggested that CXCL2 can up-regulate the expression of lnc-ARRDC3-1 and silencing of lnc-ARRDC3-1 can inhibit the proliferation, invasion and epithelial-mesenchymal transition (EMT) of the renal carcinoma cells in vitro. Therefore, we propose a novel mechanism of the metastasis of renal cell carcinoma: TAMs up-regulate the expression of lnc-ARRDC3-1 through secreting CXCL2 and then promote EMT in renal cell carcinoma. Our study aims to find the molecular mechanism by which CXCL2 up-regulates the expression of lnc-ARRDC3-1, and lnc-ARRDC3-1 promotes the EMT in renal cell carcinoma. This study may reveal a novel mechanism involved in the metastasis of renal carcinoma and provide a new molecular target to the renal cell carcinoma.