环状RNAs在乳腺癌中的研究进展

doi:10.3877/cma.j.issn.1674-0807.2020.03.009

环状RNAs(circRNAs)是一种新型的内源性非编码RNA及调控分子，广泛表达于各种生物体的真核转录组中。circRNAs特有的环状结构赋予其结构比线性RNA稳定、对核酸酶不敏感、保守性、组织表达特异性等性能，使其成为近年RNA领域研究的新热点。circRNAs与许多疾病，尤其是恶性肿瘤的发生、发展密切相关，并起着重要的调控作用，有望成为乳腺癌的新型生物学标志物和潜在的治疗靶点，可为肿瘤的诊断和靶向治疗提供新的思路。笔者对circRNAs的发展历程、产生机制、分类、生物学功能，及其在乳腺癌早期筛查、诊断和作用机制等的研究进展进行了全面综述，以期为乳腺癌的早期筛查、诊断、治疗及研究提供新的方向。

关键词: 乳腺肿瘤, 微RNAs, 基因表达调控, 环状RNAs

图1 环状RNAs发展历程中重要发现时间表^{[6,7,8,12,13,20,21,22,23,24,25,26,27,28,29]}

表1 主要类型环状RNAs的特征^[31]

环状RNAs	来源	定位	连接位点	序列特征	功能
ecircRNAs	外显子	细胞质	3′-5′磷酸二酯键	参与环化的外显子带有含反向互补序列的长内含子，并可选择性环化	微RNAs"海绵"；与RNA结合蛋白作用；参与翻译
ciRNAs	内含子	细胞核	3′-5′磷酸二酯键	5′剪切位点含有富集7个GU的基序，3′分支位点含有富集11个C的基序	调控基因转录
eIcircRNAs	外显子-内含子	细胞核	3′-5′磷酸二酯键	参与环化的外显子带有含反向互补序列的长内含子，并可选择性环化	调控基因转录

表1 主要类型环状RNAs的特征^[31]

环状RNAs	来源	定位	连接位点	序列特征	功能
ecircRNAs	外显子	细胞质	3′-5′磷酸二酯键	参与环化的外显子带有含反向互补序列的长内含子，并可选择性环化	微RNAs"海绵"；与RNA结合蛋白作用；参与翻译
ciRNAs	内含子	细胞核	3′-5′磷酸二酯键	5′剪切位点含有富集7个GU的基序，3′分支位点含有富集11个C的基序	调控基因转录
eIcircRNAs	外显子-内含子	细胞核	3′-5′磷酸二酯键	参与环化的外显子带有含反向互补序列的长内含子，并可选择性环化	调控基因转录

表2 乳腺癌组织中的环状RNAs

年份	环状RNAs	调控	"海绵"作用靶标	功能	参考文献
2015	circRNA_1093	上调	miRNA-342-3p	致癌基因	[45]
2015	circ-Foxo3	下调	miRNA-22/ miRNA-136/ miRNA-138	肿瘤抑制因子	[48]
2016	circ-Amotl1	上调	c-myc基因、miRNA-4753、miRNA-6809	致癌基因	[37]
2016	hsa_circ_103110	上调	－	生物学标志物	[42]
2016	hsa_circ_104821	上调	－	生物学标志物	[42]
2016	hsa_circ_104689	上调	－	生物学标志物	[42]
2016	hsa_circ_006054	下调	－	生物学标志物	[42]
2016	hsa_circ_100219	下调	－	生物学标志物	[42]
2017	hsa_circ_0001982	上调	miRNA-143	致癌基因	[44]
2017	circGFRA1	上调	miRNA-34a	致癌基因/生物学标志物	[47]
2017	circ-ABCB10	上调	miRNA-1271	致癌基因	[46]
2017	circVRK1	下调	－	肿瘤抑制因子	[49]
2017	hsa_circ_0108942	上调	－	生物学标志物	[44]
2017	hsa_circ_0068033	下调	－	生物学标志物	[44]
2018	hsa_circ_0001785	上调	－	生物学标志物	[43]
2018	circ_0005230	上调	miRNA-618	致癌基因/生物学标志物	[50]
2018	circRNA-000911	上调	miRNA-449a	致癌基因	[51]
2018	hsa_circ_0008039	上调	miRNA-432-5p	致癌基因	[52]
2018	hsa_circ_0052112	上调	miRNA-125a-5p	致癌基因	[53]
2018	hsa_circ_0001846	上调	miRNA-661或MTA1	致癌基因	[54]
2018	circIRAK3	上调	miRNA-3607	致癌基因	[55]
2018	hsa_circ_0007294	上调	miRNA-148a-3p、miRNA-152-3p、转录因子USF1	致癌基因	[56]
2019	OIP5-AS1	上调	miRNA-129-5p	致癌基因	[57]
2019	circAGFG1	上调	miRNA-195-5p	致癌基因	[58]

表2 乳腺癌组织中的环状RNAs

年份	环状RNAs	调控	"海绵"作用靶标	功能	参考文献
2015	circRNA_1093	上调	miRNA-342-3p	致癌基因	[45]
2015	circ-Foxo3	下调	miRNA-22/ miRNA-136/ miRNA-138	肿瘤抑制因子	[48]
2016	circ-Amotl1	上调	c-myc基因、miRNA-4753、miRNA-6809	致癌基因	[37]
2016	hsa_circ_103110	上调	－	生物学标志物	[42]
2016	hsa_circ_104821	上调	－	生物学标志物	[42]
2016	hsa_circ_104689	上调	－	生物学标志物	[42]
2016	hsa_circ_006054	下调	－	生物学标志物	[42]
2016	hsa_circ_100219	下调	－	生物学标志物	[42]
2017	hsa_circ_0001982	上调	miRNA-143	致癌基因	[44]
2017	circGFRA1	上调	miRNA-34a	致癌基因/生物学标志物	[47]
2017	circ-ABCB10	上调	miRNA-1271	致癌基因	[46]
2017	circVRK1	下调	－	肿瘤抑制因子	[49]
2017	hsa_circ_0108942	上调	－	生物学标志物	[44]
2017	hsa_circ_0068033	下调	－	生物学标志物	[44]
2018	hsa_circ_0001785	上调	－	生物学标志物	[43]
2018	circ_0005230	上调	miRNA-618	致癌基因/生物学标志物	[50]
2018	circRNA-000911	上调	miRNA-449a	致癌基因	[51]
2018	hsa_circ_0008039	上调	miRNA-432-5p	致癌基因	[52]
2018	hsa_circ_0052112	上调	miRNA-125a-5p	致癌基因	[53]
2018	hsa_circ_0001846	上调	miRNA-661或MTA1	致癌基因	[54]
2018	circIRAK3	上调	miRNA-3607	致癌基因	[55]
2018	hsa_circ_0007294	上调	miRNA-148a-3p、miRNA-152-3p、转录因子USF1	致癌基因	[56]
2019	OIP5-AS1	上调	miRNA-129-5p	致癌基因	[57]
2019	circAGFG1	上调	miRNA-195-5p	致癌基因	[58]

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Research progress of circular RNAs in breast cancer

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Research progress of circular RNAs in breast cancer