环状RNA在肝细胞癌发生发展及诊疗中的作用

苗淑莹; 杨军; 管文燕; 张标; 何璐; 樊智文

doi:10.3969/j.issn.1001-5256.2023.08.033

环状RNA在肝细胞癌发生发展及诊疗中的作用

DOI: 10.3969/j.issn.1001-5256.2023.08.033

南京大学医学院附属鼓楼医院病理科，南京 210008

基金项目:

国家自然科学基金 (81700554);

国家自然科学基金 (82170592)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：苗淑莹负责课题设计，资料分析，撰写论文；杨军、管文燕、张标、何璐参与修改论文；樊智文负责拟定写作思路，修改论文并最后定稿。

详细信息

通信作者:
樊智文，fanzhiwenfff@126.com (ORCID：0000-0002-3465-4622)

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出版历程
- 收稿日期: 2022-10-27
- 录用日期: 2022-12-17
- 出版日期: 2023-08-20

Role of circular RNA in the development, progression, diagnosis, and treatment of hepatocellular carcinoma

Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China

Research funding:

The National Natural Science Foundation of China (81700554);

The National Natural Science Foundation of China (82170592)

More Information

Corresponding author: FAN Zhiwen, fanzhiwenfff@126.com (ORCID: 0000-0002-3465-4622)

摘要

摘要: 肝细胞癌(HCC)作为原发性肝癌最常见的类型，是一种具有侵袭性且致命的恶性肿瘤，其发生发展是一个多基因参与、多步骤、多阶段的过程。环状RNA(circRNA)作为一类内源性非编码RNA，主要通过吸附微小RNA(miRNA)或者RNA结合蛋白(RBP)发挥“海绵作用”，进而调控下游靶基因表达。本文全面介绍了circRNA在HCC信号转导、免疫、代谢、耐药、HBV相关HCC中的作用及意义，及其作为HCC的生物标志物或治疗靶点的潜在价值，为HCC的诊断和治疗提供新思路。
- RNA, 环状 /
- 癌, 肝细胞 /
- 诊断 /
- 治疗学
Abstract: As the most common type of primary liver cancer, hepatocellular carcinoma (HCC) is an invasive and fatal malignant tumor, and its development and progression involve multiple genes, steps, and stages. Circular RNA (circRNA), as a class of endogenous non-coding RNAs, mainly acts as a sponge by absorbing microRNA or RNA-binding proteins to regulate the expression of downstream target genes. This article comprehensively introduces the role and significance of circRNA in signal transduction, immunity, metabolism, drug resistance, and hepatitis B virus-related HCC and its potential value as a biomarker or therapeutic target for HCC, so as to provide new ideas for the diagnosis and treatment of HCC.
- RNA, Circular /
- Carcinoma, Hepatocellular /
- Diagnosis /
- Therapeutics

HTML全文

表 1 circRNA在HCC中的生物学功能

Table 1. The biological function of circRNA in HCC

circRNA	表达	生物学功能	机制	文献
circASAP1	上调	促进细胞增殖、侵袭、转移，介导肿瘤相关巨噬细胞浸润	miR-326/miR-532-5p /MAPK1轴、miR-326/miR-532-5p-CSF-1轴	[6]
circGprc5a	上调	促进细胞增殖	miR-1283/YAP1/TEAD1轴	[7]
circ_0061395	上调	促进细胞增殖、侵袭、转移	miR-1182/SPOCK1轴	[8]
circ-STIL	上调	促进细胞增殖、侵袭、转移，抑制细胞凋亡	miR-345-5p/AQP3轴	[9]
circEIF3I	上调	促进细胞增殖、上皮-间质转化、转移、侵袭，抑制细胞凋亡	miR -526b-5p-HGF/c-Met轴	[10]
circ_0011232	上调	促进细胞增殖、集落形成、转移和侵袭，抑制细胞凋亡	miR-503-5p/AKT3轴	[11]
circCBFB	上调	促进细胞增殖和自噬，抑制细胞凋亡	miR-424-5p/ATG14轴	[12]
hsa_circ_0062682	上调	促进集落形成、转移、增殖，影响索拉非尼敏感性	RBP YBX1相互作用	[13]
SCD-circRNA2	上调	促进细胞增殖、侵袭、转移	RBP RBM3相互作用	[14]
circPTTG1IP	下调	抑制细胞增殖、集落形成、侵袭	miR-16-5p/RNF125/JAK1轴	[15]
circRNA DOCK1	上调	干扰circRNA DOCK可以抑制HCC细胞增殖、侵袭和转移	miR-654-5p/SMAD2轴	[16]
circITCH	下调	抑制细胞增殖、转移、侵袭，促进细胞凋亡	miR-184	[17]
circFGGY	下调	抑制细胞增殖、侵袭和上皮-间质转化	miR-545-3p/Smad7轴	[18]
circ-BANP	上调	抑制细胞增殖、转移和上皮-间质转化	与let-7f-5p相互作用，TLR4/STAT3轴	[19]
circDLC1	下调	抑制细胞增殖、转移	与HuR相互作用，circDLC1-HuR-MMP1轴	[20]
circRHOT1	上调	促进细胞增殖、侵袭、转移	NRF26 TIP60转录调控	[21]

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表 2 HCC中circRNA的表达及功能

Table 2. Expression and function of circRNA in HCC

circRNA	表达	生物学功能	机制	文献
免疫方面
circUHRF1	上调	参与免疫抑制	miR-449c-5p/TIM-3轴	[22]
circGSE1	上调	诱导Tregs扩增，促进HCC发展	miR324-5p/TGFBR1/Smad3轴	[23]
hsa_circ_0003410	上调	增加M2/M1巨噬细胞的比率，促进HCC发展	miR-139-3p/CCL5轴	[24]
hsa_circ_0074854	上调	下调hsa_circ_0074854抑制肝癌的迁移和侵袭	下调hsa_circ_0074854与HuR相互作用和抑制外泌体介导的巨噬细胞M2极化	[25]
代谢方面
circMAT2B	上调	增强糖酵解，促进HCC发展	miR-338-3p/PKM2轴	[26]
circ-SPECC1	下调	在氧化应激条件下促进细胞增殖，抑制细胞凋亡	海绵化miR-33a调节TGF-β2和自噬	[27]
circ_0091579	上调	抑制细胞增殖、迁移、侵袭和糖酵解	miR-490-5p/CASC3轴	[28]
circRPN2	下调	抑制有氧糖酵解和转移	加速ENO1降解和调节miR-183-5p/FOXO1轴	[29]
circ-CFH	上调	促进细胞增殖、迁移、侵袭和糖酵解	miR-377-3p/RNF38轴	[30]
hsa_circ_0001806	上调	促进细胞增殖、转移和糖酵解，抑制细胞凋亡	miR-125b/HK2轴	[31]
耐药方面
circ-001241	上调	调节索拉非尼耐药	miR-21-5p/TIMP3轴	[32]
circARNT2	上调	调节顺铂耐药	miR-155-5p/PDK1轴	[33]
hsa_circRNA_102049	下调	调节索拉非尼耐药	hsa-miR-214-3p/RELE	[34]
circTMEM181	上调	调节抗PD-1耐药	ATP-腺苷途径	[35]
circUBE2D2	上调	促进糖酵解和索拉非尼的耐药	miR-889-3p/LDHA轴	[36]
circFOXM1	上调	调控索拉非尼耐药	miR-1324/MECP2	[37]
circFBXO11	上调	调节奥沙利铂耐药	miR-605/FOXO3/ABCB1轴	[38]
HBV相关HCC
circRNA1002	下调	血清生物标志物	激素通路与细胞-细胞相互作用过程	[39]
circBACH1	上调	促进HBV复制、细胞增殖和转移	miR-200a-3p/MAP3K2	[40]
circ_0027089	上调	促进细胞增殖、转移和侵袭，抑制细胞周期阻滞和凋亡	miR-136-5p/NACC1	[41]
circ-RNF13	上调	促进细胞增殖、集落形成、转移和侵袭，抑制细胞凋亡	miR-424-5p/TGIF2	[42]
HBV_circ_1	上调	促进细胞增殖、转移和侵袭，抑制细胞凋亡	与周期蛋白依赖性激酶1相互作用	[43]

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表 3 circRNA作为HCC诊断和预后的生物标志物

Table 3. circRNA as a biomarker for the diagnosis and prognosis of HCC

circRNA	生物样本	生物标志物相关性	文献
hsa_circ_0028861	血清	诊断	[44]
hsa_circ_0001821	血浆	诊断	[45]
circ_0064286	血清	诊断	[46]
hsa_circ_0006091	HCC组织	诊断	[48]
circ_0000437	血清、HCC组织	诊断、预后	[49]
circMED27	血清	预测乐伐替尼耐药、预后	[50]
hsa_circ_0005986	血清、HCC组织	预后	[51]
CSMARCA5	HCC组织	预后	[52]
circRNA_101237	血清、HCC组织	预后	[53]

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