MiR-3162-5p通过激活Ras信号通路促进宫颈鳞癌细胞EMT的作用及机制研究

Cervical squamous cell carcinoma (CSCC) is the most common malignant tumor of the female reproductive system, and CSCC metastasis can lead to poor prognosis. Epithelial-mesenchymal transition (EMT) is the key step in CSCC metastasis and is regulated by microRNA and Ras signaling pathways. In previous studies, we found that miR-3162-5p, whose directed target gene was RASA4, could promote EMT in CSCC cells. Other previous studies have shown that RASA4 inhibited the downstream Ras signaling pathways, and was specifically low expressed in CSCC. In conclusion, we deduce that miR-3162-5p can activate Ras signaling pathway to promote EMT process in CSCC cells by inhibiting RASA4, but its in-depth mechanism remains to be confirmed. By studying on cell experiments, animal experiments and clinical analysis, our research aims to investigate the specific effects of miR-3162-5p, RASA4 and Ras signaling pathways in the EMT process of CSCC, which could provide the experimental basis for molecular diagnosis and targeted therapy of CSCC .

宫颈鳞癌（cervical squamous cell carcinoma，CSCC）是女性生殖系统最常见的恶性肿瘤，肿瘤转移可导致不良预后。上皮-间充质转换（epithelial-mesenchymal transition，EMT）是CSCC转移的关键步骤，受microRNA和Ras信号通路调控。前期研究我们发现，miR-3162-5p可促进CSCC细胞的EMT过程，RASA4是其靶基因。前人研究显示RASA4可抑制Ras信号下游通路，并在CSCC癌组织中特异低表达。综上推断miR-3162-5p可通过抑制RASA4而激活Ras通路促进CSCC细胞EMT过程，但深入机制仍待证实。本项目拟通过细胞实验、动物实验、临床分析等多方位研究，探讨miR-3162-5p、RASA4和Ras信号通路对CSCC细胞EMT过程的具体作用，为CSCC的分子诊断和靶向治疗提供实验基础。

肿瘤，肿瘤转移可导致不良预后。上皮-间充质转换（epithelial-mesenchymal transition，EMT）是CSCC转移的关键步骤，受microRNA和Ras信号通路调控。前期研究我们发现，miR-3162-5p可促进CSCC细胞的EMT过程，RASA4是其靶基因。前人研究显示RASA4可抑制Ras信号下游通路，并在CSCC癌组织中特异低表达。本研究通过实验证实了 miR-3162-5p对宫颈鳞癌的促增殖、侵袭、EMT作用；并实验证实了RAS信号通路中重要的负调节因子RASA4是miR-3162-5p的靶基因；同时证实了miR-31625p可通过抑制RASA4促进宫颈癌细胞增殖；实验证实了RASA4可通过下游通路HIF1抑制宫颈癌细胞的增殖。为CSCC的分子诊断和靶向治疗提供了实验基础。