环状RNA FBXW7在三阴乳腺癌中的表达及其临床意义

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HCC1806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。

Expression of circular RNA FBXW7 in triple-negative breast cancer and its clinical significance

Background and Aims: Circular RNAs are a class of important regulatory elements that are involved in many cancer processes. It was reported that circular RNA FBXW7 (RNA circFBXW7) plays a tumor suppressor role in glioma through encoding a novel protein. However, its function and action mechanism in triple-negative breast cancer (TNBC) is still unclear. Therefore, this study was conducted to investigate the role of circFBXW7 in TNBC and its clinical significance.  Methods: The fresh specimens of tumor tissues from 240 TNBC patients and their clinical data were collected. the related prognosis data were also collected. The expression levels of circFBXW7 in these samples were detected by qRT-PCR, the relationship between circFBXW7 expression and the prognosis of TNBC patients was analyzed by Kaplan-Meier method, and the prognostic factors for TNBC patients were determined by Cox regression analysis. In TNBC cell lines MDA-MB-231 and HCC1806 after circFBXW7 over-expression, the changes in proliferation, migration and invasion abilities as well as miR-197-3p expression were examined by CCK8 assay and Transwell chamber assay. In above two types of cells after circFBXW7 knockdown and simultaneous miR-197-3p inhibitor transfection, the changes in proliferation and invasion abilities were measured by colony formation assay and Transwell chamber assay, respectively.  Results: The average expression level of circFBXW7 in the tumor tissues from the 240 TNBC patients was 1.043±0.268. Using 1.043 as a threshold value, the results of grouped analysis showed that both overall survival and disease-free survival in patients with low circFBXW7 expression were significantly shorter than those in patients with high circFBXW7 expression (both P<0.05); the circFBXW7 expression, histological grade and TNM classification were independent influencing factors for the prognosis of TNBC patients (all P<0.05). The results of cytological studies showed that the proliferation, migration and invasion abilities as well as the miR-197-3p expression levels of MDA-MB-231 and HCC1806 cells were significantly reduced after circFBXW7 over-expression (all P<0.05); the increased proliferation and invasion abilities of MDA-MB-231 and HCC1806 cells induced by circFBXW7 knockdown were reversed by simultaneous miR-197-3p inhibitor transfection (both P<0.05). Conclusion: The circFBXW7 expression plays a suppressing role in TNBC, and the mechanism may be associated with its competitive binding miR-197-3p and thereby inhibit the proliferation and invasion of TNBC cells. It may be a novel prognostic biomarker and a potential therapeutic target for TNBC.