环状RNA对肝细胞癌的血管生成、免疫细胞和能量代谢调控的研究进展

Research progress on circular RNAs in the regulation of angiogenesis,immune cells,and energy metabolism in hepatocellular carcinoma

肝细胞癌(HCC)是原发性肝癌最主要的病理类型,占肝癌患者总数的75%~85%。HCC的发生发展与编码RNA和非编码RNA的调节功能密切相关,其中环状RNA(circRNA)代表了一类新的内源性非编码RNA。circRNA也是一种共价闭环RNA,它通过对前体mRNA的反向剪接环化形成。与线性RNA相比,circRNA没有5'-末端帽子和3'-末端poly A尾巴结构,可以调节哺乳动物中的基因表达。circRNA的结构保守且稳定,对核酸外切酶具有更高的耐受性。在HCC中,circRNA已被证明可以调节肿瘤细胞增殖、迁移、侵袭和细胞死亡抵抗力。它们在调节血管生成、基因组不稳定、免疫监视和代谢转换方面的作用正在显现。但circRNA在HCC中所涉相关机制的细节仍然难以解析,尤其在调控HCC的血管生成、调节HCC细胞躲避免疫细胞的监测与攻击和调节细胞能量代谢为HCC细胞供能,从而引发HCC的增殖、侵袭和转移等方面。研究在HCC中起关键调控作用的circRNA,针对其靶向治疗能有望提高HCC的治疗效果,并改善患者预后。笔者就HCC中异常表达的circRNA,以及circRNA对HCC的血管生成、免疫细胞和能量代谢的调控做一综述。

Hepatocellular carcinoma(HCC)is the most prevalent pathological type of primary liver cancer,accounting for 75%to 85%of all liver cancer cases.The occurrence and development of HCC are closely associated with the regulatory functions of both coding RNAs and non-coding RNAs.Circular RNAs(circRNAs)represent a novel class of endogenous non-coding RNA.CircRNAs are covalently closed-loop RNA formed by back-splicing of precursor mRNAs.Compared to linear RNAs,circRNAs lack the 5'-end cap and 3'-end poly A tail structure but can regulate gene expression in mammals.CircRNAs are structurally conserved and stable and have a higher tolerance to exonucleases.In HCC,circRNAs have been demonstrated to regulate tumor cell proliferation,migration,invasion,and resistance to cell death.Their roles in regulating angiogenesis,genomic instability,immune surveillance,and metabolic reprogramming are also becoming evident.However,the detailed mechanisms involving circRNAs in HCC remain elusive,especially regarding how circRNAs regulate angiogenesis in HCC,modulate the evasion of HCC cells from the detection and attack of the immune cells,and regulate cellular energy metabolism to provide energy for HCC cell proliferation,invasion,and metastasis.Studying circRNAs that play critical regulatory roles in HCC may hold promise for targeted therapies,thereby enhancing treatment effectiveness and improving patient prognosis.In this review,the authors summarize the abnormal expression of circRNAs in HCC and their regulatory roles in angiogenesis,immune cell interactions,and energy metabolism for HCC cells.