circFBXW7 Inhibits Malignant Progression by Sponging miR-197-3p and Encoding a 185-aa Protein in Triple-Negative Breast Cancer
circFBXW7 Inhibits Malignant Progression by Sponging miR-197-3p and Encoding a 185-aa Protein in Triple-Negative Breast Cancer
复制标题
circFBXW7 通过海绵 miR-197-3p 并编码三阴性乳腺癌中的 185 个氨基酸蛋白抑制恶性进展
DOI：
10.1016/j.omtn.2019.07.023
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发表时间：
2019-12-06
影响因子：
8.8
通讯作者：
Tang, Hailin
中科院分区：
文献类型：
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作者：
Ye, Feng;Gao, Guanfeng;Tang, Hailin
越来越多的证据表明，环状 RNA (circRNA) 是多种癌症进展中各种生物学功能的重要调节因子。据报道，含有 7 (circFBXW7) (hsa_circ_0001451) 的圆形 F-box 和 WD 重复结构域可通过在神经胶质瘤中编码一种新蛋白来充当肿瘤抑制因子；然而，其在三阴性乳腺癌（TNBC）中的功能和机制仍然难以捉摸。在当前的研究中，我们通过 qRT-PCR 验证了 circFBXW7 在 TNBC 细胞系中下调，并发现 circFBXW7 的低表达与较差的临床结果相关。 circFBXW7表达与肿瘤大小、淋巴结转移呈负相关，是TNBC患者的独立预后因素。我们进行了细胞增殖、集落形成、transwell、伤口愈合和小鼠异种移植测定，以确认 circFBXW7 的功能。在体外和体内实验中，circFBXW7 的过表达均明显抑制细胞增殖、迁移和肿瘤生长。荧光素酶报告基因检测和 RNA 免疫沉淀检测显示，circFBXW7 作为 miR-197-3p 的海绵，通过上调 FBXW7 表达来抑制 TNBC 生长和转移。此外，circFBXW7编码的FBXW7-185aa蛋白通过增加FBXW7的丰度并诱导c-Myc降解来抑制TNBC细胞的增殖和迁移能力。总之，我们的研究表明，circFBXW7 海绵 miR-197-3p 并编码 FBXW7-185aa 蛋白，通过上调 FBXW7 表达来抑制 TNBC 进展。因此，circFBXW7可以作为TNBC的治疗靶点和预后生物标志物。
Accumulating evidence indicates that circular RNAs (circRNAs) are vital regulators of various biological functions involved in the progression of multiple cancers. Circular F-box and WD repeat domain containing 7 (circFBXW7) (hsa_circ_0001451) has been reported to act as a tumor suppressor by encoding a novel protein in glioma; however, its functions and mechanisms in triple-negative breast cancer (TNBC) remain elusive. In the current study, we validated by qRT-PCR that circFBXW7 was downregulated in TNBC cell lines and found that low expression of circFBXW7 was associated with poorer clinical outcomes. circFBXW7 expression was negatively correlated with tumor size and lymph node metastasis, and it was an independent prognostic factor for TNBC patients. We performed cell proliferation, colony formation, transwell, wound-healing, and mouse xenograft assays to confirm the functions of circFBXW7. Overexpression of circFBXW7 obviously inhibited cell proliferation, migration, and tumor growth in both in vitro and in vivo assays. Luciferase reporter assays and RNA immunoprecipitation assays revealed that circFBXW7 serves as a sponge of miR-197-3p and suppresses TNBC growth and metastasis by upregulating FBXW7 expression. In addition, the FBXW7-185aa protein encoded by circFBXW7 inhibited the proliferation and migration abilities of TNBC cells by increasing the abundance of FBXW7 and inducing c-Myc degradation. In summary, our research demonstrated that circFBXW7 sponges miR-197-3p and encodes the FBXW7-185aa protein to suppress TNBC progression through upregulating FBXW7 expression. Thus, circFBXW7 may act as a therapeutic target and prognostic biomarker for TNBC.