低氧微环境是肝癌的固有特征，可通过多种信号途径促进肝癌侵袭转移。近年来发现RNA甲基化修饰在肝癌转移中起重要作用，但低氧微环境是否可以通过调控m5C甲基化促进肝癌细胞恶性化程度增加尚不清楚。通过前期研究实验证实：⑴m5C甲基化总体修饰在低氧环境下更高；⑵m5C甲基化修饰关键酶NSUN5在低氧环境下上调表达；⑶NSUN5能够上调IL-6的mRNA表达；⑷IL-6mRNA3'- UTR在低氧微环境下发生m5C甲基化。基于以上结论我们提出假设：低氧微环境通过上调NSUN5表达后介导IL-6的3'-UTR m5C甲基化进而增强其mRNA稳定性-促进STAT3信号通路激活,从而导致了肝癌细胞恶性化程度增加。本课题拟从分子、细胞、动物模型和临床样本四个层面验证上述假设，旨在丰富低氧微环境对促进肝癌恶化的认识，为肝癌的临床诊治提供新的思路。

As an inherent feature of hepatocellular carcinoma (HCC), hypoxic microenvironment can accelerate the invasion and metastasis of HCC through a variety of signal pathways. While it has been revealed in recent years that RNA methylation plays a crucial role in the metastasis of HCC, it remains yet unclear whether hypoxia microenvironment can exacerbate the malignancy of HCC cells by regulating m5C methylation. Our previous studies have confirmed that: (1) the modification m5C methylation level of HCC cell lines was increased in hypoxia environment; (2) NSUN5, a key enzyme of m5C methylation, was up-regulated in hypoxia environment; (3) NSUN5 could up-regulate the mRNA expression of IL-6; and (4) the m5C methylation level of IL-6 mRNA 3'- UTR was up-regulated in hypoxia environment. Based on the findings above, a hypothesis is put forward in this article that, by up-regulating the expression of NSUN5, hypoxia microenvironment can enhance the mRNA stability of IL-6 and thus the activation of STAT3 signaling pathway, finally resulting in a raised malignant degree of HCC cells. Furthermore, this hypothesis is to be verified from four aspects: molecular, cellular, animal model and clinical samples, so as to enrich our knowledge of the role of hypoxic microenvironment in the deterioration of HCC, which is expected to shed some light on the clinical diagnosis and treatment of HCC.