Department of Head-Neck and Breast Surgery, Yuebei People's Hospital of Shantou University, Shaoguan, Guangdong, China.
Operation room, Yuebei People's Hospital of Shantou University, Shaoguan, Guangdong, China.
Clin Breast Cancer. 2023 Apr;23(3):291-301. doi: 10.1016/j.clbc.2022.12.014. Epub 2022 Dec 23.
Breast cancer (BC) has posed a fatal threat to women's lives and the search for new methods of diagnosis and treatment is an important way to break the bottleneck of high mortality in BC. Circular RNAs (circRNAs) have been confirmed to be aberrantly expressed in several types of cancers, and this study is intended to elucidate the role and mechanism of circ_0108942 in BC.
The levels of circ_0108942, microRNA-1178-3p (miR-1178-3p), and transmembrane p24 trafficking protein 3 (TMED3) were measured using real-time quantitative polymerase chain reaction (RT-qPCR) or western blot. Meanwhile, the cell proliferation, migration, invasion, angiopoiesis, and apoptosis were analyzed using 5-ethynyl-2'-deoxyuridine (EdU), transwell, tubule formation, and flow cytometry assays. Protein levels were determined by western blot. In addition, we used dual-luciferase reporter and RNA pull-down assays to identify the interplay between miR-1178-3p and circ_0108942 or TMED3. Lastly, the impact of circ_0108942 on the growth of BC tumors in vivo was analyzed by xenograft models.
Circ_0108942 and TMED3 were notably upregulated in BC, and the miR-1178-3p was downregulated. Functionally, silencing circ_0108942 suppressed cell proliferation, migration, invasion and promoted apoptosis in BC cells. In mechanism, circ_0108942 regulated TMED3 expression by sponging miR-1178-3p. Meanwhile, circ_0108942 knockdown also greatly constrained tumor growth in vivo.
Circ_0108942 boosted BC progression by regulating miR-1178-3p and thus upregulating TMED3.
乳腺癌（BC）对女性的生命构成了致命威胁，寻找新的诊断和治疗方法是打破 BC 高死亡率瓶颈的重要途径。环状 RNA（circRNA）已被证实在几种类型的癌症中异常表达，本研究旨在阐明 circ_0108942 在 BC 中的作用和机制。
采用实时定量聚合酶链反应（RT-qPCR）或 Western blot 检测 circ_0108942、微小 RNA-1178-3p（miR-1178-3p）和跨膜 p24 转运蛋白 3（TMED3）的水平。同时，采用 5-乙炔基-2'-脱氧尿苷（EdU）、Transwell、管形成和流式细胞术分析细胞增殖、迁移、侵袭、血管生成和凋亡。Western blot 法测定蛋白水平。此外，我们还利用双荧光素酶报告基因和 RNA 下拉实验鉴定 miR-1178-3p 与 circ_0108942 或 TMED3 之间的相互作用。最后，通过异种移植模型分析 circ_0108942 对体内 BC 肿瘤生长的影响。
circ_0108942 和 TMED3 在 BC 中显著上调，miR-1178-3p 下调。功能上，沉默 circ_0108942 可抑制 BC 细胞的增殖、迁移、侵袭，促进凋亡。在机制上，circ_0108942 通过海绵吸附 miR-1178-3p 调节 TMED3 的表达。同时，circ_0108942 敲低也显著抑制体内肿瘤的生长。
circ_0108942 通过调节 miR-1178-3p 进而上调 TMED3，促进 BC 的进展。
