目的:探讨山柰酚通过调控circFBXW7对宫颈癌SiHa细胞增殖、迁移及侵袭的影响。方法:采用山柰酚低、中、高剂量（15、30、60 μmol/L）处理SiHa细胞24 h，未经处理的SiHa细胞为对照组。CCK-8检测山柰酚对SiHa细胞增殖的影响，Transwell检测山柰酚对SiHa细胞迁移和侵袭的影响，并采用实时荧光定量聚合酶链反应检测SiHa细胞中circFBXW7的表达量。pcDNA、pcDNA-circFBXW7分别转染至SiHa细胞，si-NC、si-circFBXW7分别转染至SiHa细胞后加入60 μmol/L山柰酚处理24 h，考察circFBXW7及其敲除circFBXW7对SiHa细胞增殖、迁移、侵袭的影响，并采用Western Blot检测 E-钙黏蛋白、 N-钙黏蛋白的表达水平。 结果:与对照组相比，山柰酚低、中、高剂量组的细胞增殖、迁移及侵袭能力均下降（均 P<0.05），且呈剂量相关性，circFBXW7的表达量升高（ P<0.05）。转染pcDNA-circFBXW7后，circFBXW7表达量升高（ P<0.05），同时促进山柰酚对SiHa细胞的增殖、迁移及侵袭（均 P<0.05）；转染si-circFBXW7后，circFBXW7表达量降低（ P<0.05），同时抑制山柰酚对SiHa细胞的增殖、迁移及侵袭（均 P<0.05）可减弱增殖、迁移及侵袭的抑制作用。与对照组相比，山柰酚低、中、高剂量组的 E-钙黏蛋白表达上调， N-钙黏蛋白表达下调（均 P<0.05），且呈剂量相关性；SiHa细胞转染pcDNA-circFBXW7后， E-钙黏蛋白的表达上升， N-钙黏蛋白的表达降低（均 P<0.05）；转染si-circFBXW7后， E-钙黏蛋白的表达降低， N-钙黏蛋白的表达上升（均 P<0.05）。 结论:山柰酚可通过促进circFBXW7表达而减弱SiHa细胞的增殖、迁移及侵袭能力。

As a newly discovered type of RNA,circular RNAs (circRNAs) are widespread throughout the eukaryotic genome.The expression of circRNAs is regulated by both cis-elements and trans-factors,and the expression pattern of circRNAs is cell type-and disease-specific.Similar to other types of non-coding RNAs,functions of circRNAs are also versatile.CircRNAs have been reported previously to function as microRNA (miRNA) sponges,protein sponges,coding RNAs or scaffolds for protein complexes.Recently,several circRNAs have been reported to play important roles in human malignancies,including glioma.Here,we reviewed several reports related to circRNAs and glioma,as well as the potential diagnostic and therapeutic applications of circRNAs in brain cancer.In general,some circRNAs,such as circSMARCA5 and circCFH,are found to be expressed in a glioma-specific pattern,these circRNAs may be used as tumor biomarkers.In addition,some circRNAs have been found to play oncogenic roles in glioma (e.g.,circNFIX and circNT5E),whereas others have been reported to function as tumor suppressors (e.g.,circFBXW7 and circSHPRH).Furthermore,circRNA is a good tool for protein expression because of its higher stability compared to linear RNAs.Thus,circRNAs may also be an ideal choice for gene/protein delivery in future brain cancer therapies.There are some challenges in circRNA research in glioma and other diseases.Research related to circRNAs in glioma is comparatively new and many mysteries remain to be solved.

背景与目的:环状RNA(circRNA)是参与多种癌症进程的重要调节因子.据报道,环状RNA FBXW7(circFBXW7)在胶质瘤中通过编码一种新蛋白发挥抑癌作用.然而,其在三阴性乳腺癌(TNBC)中的功能和机制尚不明确.本研究探讨了circFBXW7在TNBC中的作用及其临床意义.方法:收集240例TNBC患者的新鲜癌组织及临床资料,通过qRT-PCR检测癌组织中circFBXW7的表达,用Kaplan-Meier法分析TNBC患者circFBXW7表达水平与预后的关系,并用Cox回归方法分析TNBC患者的预后因素.用CCK8实验、Transwell实验、qRT-PCR观察TNBC细胞株MDA-MB-231和HCC 1806过表达circFBXW7后增殖与迁移、侵袭能力以及miR-197-3p表达的变化,在上述两种细胞中,敲除circFBXW7并转染miR-197-3p抑制剂后,用Transwell实验与克隆形成实验分析增殖与侵袭能力的变化.结果:240例TNBC患者癌组织标本中circFBXW7的平均表达水平为1.043±0.268,以1.043为临界值分组生存分析显示,circFBXW7低表达患者的总生存期和无病生存期明显短于circFBXW7高表达患者(均P＜0.05);circFBXW7表达以及组织学分级、TNM分期为TNBC患者预后的独立影响因素(均P＜0.05).细胞实验显示,过表达circFBXW7后,MDA-MB-231和HCC1806细胞的增殖、迁移与侵袭能力以及miR-197-3p表达均明显降低(均P＜0.05);共转染miR-197-3p抑制剂可逆转由于敲除circFBXW7所致的MDA-MB-231和HCC1806细胞的增殖与侵袭能力的增强(均P＜0.05).结论:circFBXW7的表达在TNBC中发挥抑癌作用,机制可能与其竞争性吸附miR-197-3p,从而抑制TNBC细胞的增殖与侵袭有关,FBXW7可能是一种新型TNBC预后生物标志物及潜在治疗靶标.