Li Zehuan, Chen Zhanghan, Feng Yanling, Hu Guohua, Jiang Ying
Department of General Surgery, Zhongshan Hospital, Fudan University Shanghai, China.
Department of Pathology, Shanghai Public Health Clinical Center, Fudan University Shanghai, China.
Am J Transl Res. 2020 Jun 15;12(6):2585-2599. eCollection 2020.
Numerous studies have found that circular RNAs (circRNA) can serve as competing endogenous RNA (ceRNA) in cancer progression while the expression profiles and functions of competitive endogenous circRNAs (ce-circRNAs) in breast cancer (BC) have not been determined.
Six pairs of tissue samples were selected to perform ceRNA microarray, and The Cancer Genome Atlas (TCGA) data was also included to explore the ce-circRNA profiling of BC. The expression of one of the top upregulated circRNAs, circMMP11, was confirmed by qRT-PCR in both breast cancer cell lines and tissues. We also analyzed the clinical impact of circMMP11 on BC. To explore the functions of circMMP11 in BC, experiments referring to cell proliferation and migration were performed. The regulatory effect of circMMP11 on miRNA and its target genes was explored to confirm its ce-circRNA mechanisms in BC.
qRT-PCR analyses verified that circMMP11 was successfully transfected and positively associated with a poorer clinicopathology of BC. The inhibition of circMMP11 suppressed cell proliferation and migration of BC. The luciferase reporter assay revealed that circMMP11 and MMP11 could bind to miR-1204 and that circMMP11 acted as a ce-circRNA by regulating the expression of MMP11 via sponging miR-1204.
The circMMP11/miR-1204/MMP11 axis regulates breast cancer progression via a competitive endogenous RNA (ceRNA) mechanism. CircMMP11 may serve as a potential therapeutic target in BC.
众多研究发现，环状RNA（circRNA）在癌症进展中可作为竞争性内源性RNA（ceRNA）发挥作用，而乳腺癌（BC）中竞争性内源性环状RNA（ce-circRNA）的表达谱和功能尚未明确。
选取6对组织样本进行ceRNA微阵列分析，同时纳入癌症基因组图谱（TCGA）数据以探究BC的ce-circRNA谱。通过qRT-PCR在乳腺癌细胞系和组织中证实上调程度最高的circRNA之一circMMP11的表达。我们还分析了circMMP11对BC的临床影响。为探究circMMP11在BC中的功能，进行了涉及细胞增殖和迁移的实验。探究circMMP11对miRNA及其靶基因的调控作用，以证实其在BC中的ce-circRNA机制。
qRT-PCR分析证实circMMP11成功转染且与BC较差的临床病理特征呈正相关。circMMP11的抑制可抑制BC细胞的增殖和迁移。荧光素酶报告基因检测显示circMMP11和MMP11可与miR-1204结合，且circMMP11通过海绵吸附miR-1204调节MMP11的表达而作为ce-circRNA发挥作用。
circMMP11/miR-1204/MMP11轴通过竞争性内源性RNA（ceRNA）机制调节乳腺癌进展。CircMMP11可能作为BC的潜在治疗靶点。
