环状RNAs作为宫颈癌潜在生物标志物及治疗靶点的研究进展

doi:10.12280/gjfckx.20200836

摘要/Abstract

摘要：

环状RNAs（circular RNAs,circRNAs）是一种无游离5′端和3′端的单链共价闭合的非编码RNA,其丰富性、稳定性和表达特异性等结构特点展现出其有成为肿瘤无创生物标志物的潜能。CircRNAs主要通过发挥微小RNA（miRNA）海绵、与RNA结合蛋白相互作用、调节mRNA稳定性及基因转录和翻译蛋白功能在多种肿瘤中差异表达并发挥重要作用。目前尚无宫颈癌早期预警特异性标志物及潜在治疗靶点,已有研究证实circRNAs差异表达在宫颈癌发生发展中信号通路及基因表达中的重要作用。CircRNAs主要通过miRNA海绵作用参与circRNA-miRNA-靶基因调节轴促进宫颈癌增殖、侵袭和转移且与肿瘤直径、临床分期、淋巴结转移及不良预后有关。

关键词: 环状RNA, 宫颈肿瘤, 生物标记,肿瘤, 细胞增殖, 治疗

Abstract:

Circular RNAs (circRNAs) are single-stranded, covalently closed noncoding RNAs without 3′ and 5′ ends. Evidence demonstrated that circRNAs are abundant, stable and able to show cell/tissue-specific expression, which structure features show potential for noninvasive molecular biomarkers of tumors. CircRNAs express differentially and play an important role in many kinds of neoplasms by miRNA sponges, interaction with RNA binding proteins, modulating the stability of mRNAs, regulating gene transcription and translation proteins. There are no specific biomarkers for early warning and potential therapeutic targets currently. Many studies have demonstrated differential expression of circRNAs function vitally on singnal pathway and gene expression in the initiation and development of cervical cancer. CircRNAs involve in circRNA-miRNA-target gene axis mainly through miRNA sponges to promote cervical cancer cell proliferation, invasion and metastasis, and associate with tumor size, clinical stage, metastatic lymph nodes and poor prognosis.

Key words: Circular RNA, Uterine cervical neoplasms, Biomarkers,tumor, Cell proliferation, Therapy

李贺同, 王伟, 郝敏. 环状RNAs作为宫颈癌潜在生物标志物及治疗靶点的研究进展[J]. 国际妇产科学杂志, 2021, 48(3): 322-327.

LI He-tong, WANG Wei, HAO Min. Progress of CircRNAs as A Promising Biomarker and Therapeutic Target for Cervical Cancer[J]. Journal of International Obstetrics and Gynecology, 2021, 48(3): 322-327.

图/表 1

参考文献 41

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circRNA	表达水平	作用机制通路	功能	参考文献
has_circ_0004771（circNRIP1）	上调	has_circ_0004771/miR-629-3p/PTP4A1/ERK1/2	促进宫颈癌细胞的增殖、侵袭和迁移;淋巴脉管间隙浸润	[16]
has_circ_0001038	上调	has_circ_0001038/miR-337-3p/CNNM3, MACC1	分别促进宫颈癌细胞的增殖、侵袭	[17]
has_circ_0018289	上调	has_circ_0018289/miR-497	促进宫颈癌细胞的增殖、侵袭和迁移	[18-19]
circRNA8924	上调	circRNA8924/miR-518d-5p/519-5p/CBX8	促进宫颈癌细胞的增殖、侵袭和迁移	[20]
circ_0067934	上调	circ_0067934/miRNA-545/EIF3C	促进宫颈癌细胞增殖、菌落形成、迁移、侵袭和EMT	[21]
has_circ_0060467（circMYBL2）	上调	has_circ_0060467/miR-361-3p	促进宫颈癌细胞增殖、侵袭和EMT过程	[22]
circ_0005576	上调	circ_0005576/miR-153-3p/KIF20A	促进细胞增殖、集落形成、迁移和侵袭	[23]
has_circ_101996	上调	has_circRNA_101996/miRNA-8075/TPX2	促进宫颈癌细胞的增殖、侵袭和迁移	[24]
circ-HIPK3	上调	circ-HIPK3/miR-338-3p/HIF-1α	促进宫颈癌细胞的增殖、侵袭和迁移	[25]
circMYLK	上调	circMYLK/miR-1301-3p/RHEB/mTOR	促进宫颈癌细胞克隆、增殖能力	[26]
circ-0033550（circ-AKT1）	上调	circ-AKT1/miR-942-5p/AKT1	促进宫颈癌细胞增殖、侵袭及EMT	[27]
has_circ_0001445（circSMARCA5）	下调	circSMARCA5/miR-620	促进宫颈癌细胞的增殖、侵袭和迁移并诱导细胞周期停滞	[28]
has_circ_0023404	上调	has_circ_0023404/miR-136/TFCP2/YAP	促进宫颈癌细胞的增殖、侵袭和迁移并诱导细胞周期停滞	[29]
has_circ_0000263	上调	has_circ_0000263/miRNA-150-5p/MDM4/p53	促进宫颈癌细胞的增殖、侵袭,影响凋亡和细胞周期	[30]
circRNA-000284	上调	circRNA-000284/miRNA-506/Snail-2	促进细胞增殖和侵袭同时使细胞周期停滞在G0/G1期	[31]
circ-ATP8A2	上调	circ-ATP8A2/miR-433/EGFR	促进宫颈癌细胞的增殖、侵袭和迁移及促进细胞凋亡	[32]
circEIF4G2	上调	circEIF4G2/miR218/HOXA1	细胞增殖、集落形成、迁移和侵袭	[33]
circ_0004214（circAMOTL1）	上调	circAMOTL1/miR-485-5p/AMOTL1	促进宫颈癌细胞增殖	[34]
has_circ_0000745	上调	has_circ_0000745/E-cadherin	促进宫颈癌细胞的增殖、侵袭和迁移	[35]
circSLC26A4	上调	QKI/circSLC26A4/miR-1287-5p/HOXA7	促进宫颈癌细胞的增殖、侵袭	[36]

circRNA	表达水平	作用机制通路	功能	参考文献
has_circ_0004771（circNRIP1）	上调	has_circ_0004771/miR-629-3p/PTP4A1/ERK1/2	促进宫颈癌细胞的增殖、侵袭和迁移;淋巴脉管间隙浸润	[16]
has_circ_0001038	上调	has_circ_0001038/miR-337-3p/CNNM3, MACC1	分别促进宫颈癌细胞的增殖、侵袭	[17]
has_circ_0018289	上调	has_circ_0018289/miR-497	促进宫颈癌细胞的增殖、侵袭和迁移	[18-19]
circRNA8924	上调	circRNA8924/miR-518d-5p/519-5p/CBX8	促进宫颈癌细胞的增殖、侵袭和迁移	[20]
circ_0067934	上调	circ_0067934/miRNA-545/EIF3C	促进宫颈癌细胞增殖、菌落形成、迁移、侵袭和EMT	[21]
has_circ_0060467（circMYBL2）	上调	has_circ_0060467/miR-361-3p	促进宫颈癌细胞增殖、侵袭和EMT过程	[22]
circ_0005576	上调	circ_0005576/miR-153-3p/KIF20A	促进细胞增殖、集落形成、迁移和侵袭	[23]
has_circ_101996	上调	has_circRNA_101996/miRNA-8075/TPX2	促进宫颈癌细胞的增殖、侵袭和迁移	[24]
circ-HIPK3	上调	circ-HIPK3/miR-338-3p/HIF-1α	促进宫颈癌细胞的增殖、侵袭和迁移	[25]
circMYLK	上调	circMYLK/miR-1301-3p/RHEB/mTOR	促进宫颈癌细胞克隆、增殖能力	[26]
circ-0033550（circ-AKT1）	上调	circ-AKT1/miR-942-5p/AKT1	促进宫颈癌细胞增殖、侵袭及EMT	[27]
has_circ_0001445（circSMARCA5）	下调	circSMARCA5/miR-620	促进宫颈癌细胞的增殖、侵袭和迁移并诱导细胞周期停滞	[28]
has_circ_0023404	上调	has_circ_0023404/miR-136/TFCP2/YAP	促进宫颈癌细胞的增殖、侵袭和迁移并诱导细胞周期停滞	[29]
has_circ_0000263	上调	has_circ_0000263/miRNA-150-5p/MDM4/p53	促进宫颈癌细胞的增殖、侵袭,影响凋亡和细胞周期	[30]
circRNA-000284	上调	circRNA-000284/miRNA-506/Snail-2	促进细胞增殖和侵袭同时使细胞周期停滞在G0/G1期	[31]
circ-ATP8A2	上调	circ-ATP8A2/miR-433/EGFR	促进宫颈癌细胞的增殖、侵袭和迁移及促进细胞凋亡	[32]
circEIF4G2	上调	circEIF4G2/miR218/HOXA1	细胞增殖、集落形成、迁移和侵袭	[33]
circ_0004214（circAMOTL1）	上调	circAMOTL1/miR-485-5p/AMOTL1	促进宫颈癌细胞增殖	[34]
has_circ_0000745	上调	has_circ_0000745/E-cadherin	促进宫颈癌细胞的增殖、侵袭和迁移	[35]
circSLC26A4	上调	QKI/circSLC26A4/miR-1287-5p/HOXA7	促进宫颈癌细胞的增殖、侵袭	[36]