Zhong Jin-Xiu, Kong Yun-Yuan, Luo Rong-Guang, Xia Guo-Jin, He Wen-Xing, Chen Xue-Zhong, Tan Wei-Wei, Chen Qing-Jie, Huang Yu-Yin, Guan Yan-Xing
Department of Breast Cancer Center/Nuclear Medicine, The Affiliated Cancer Hospital of Nanchang University, Nanchang, 330029, China.
Department of Nuclear Medicine/Radiology, The First Affiliated Hospital of Nanchang University, No. 17 Yong Wai Street, Nanchang, 330006, Jiangxi, China.
J Transl Med. 2021 Nov 3;19(1):455. doi: 10.1186/s12967-021-03114-8.
Circular RNAs (circRNAs) are pivotal regulators of various human cancers and circ-ERBB2 is abnormally expressed in breast cancer cells. However, the role and mechanism of circ-ERBB2 in HER2-positive breast cancer are still unknown.
The circ-ERBB2 expressions in the tumor tissues of HER2-positive breast cancer patients were tested using quantitative real-time PCR. The circ-ERBB2 function was investigated by cell counting kit 8 assay, Transwell, flow cytometry and Western blot. Mechanistically, fluorescence in situ hybridization, RNA immunoprecipitation, RNA pull-down and dual-luciferase reporter gene assays were conducted to confirm the interaction between circ-ERBB2 and miR-136-5p or miR-198 in HER2-positive breast cancer cells.
Circ-ERBB2 was elevated in the tumor tissues of HER2-positive breast cancer patients. Functionally, the interference with circ-ERBB2 repressed HER2-positive breast cancer cell proliferation, migration, invasion and accelerated cell apoptosis. Furthermore, the mechanistic analysis corroborated that circ-ERBB2 acted as a competing endogenous RNA for miR-136-5p or miR-198 to relieve the repressive influence of miR-136-5p or miR-198 on its target transcription factor activator protein 2C (TFAP2C). Meanwhile, in vivo assays further corroborated the oncogenic function of circ-ERBB2 in HER2-positive breast cancer.
Circ-ERBB2 accelerated HER2-positive breast cancer progression through the circ-ERBB2/miR-136-5p/TFAP2C axis or the circ-ERBB2/miR-198/TFAP2C axis.
环状RNA（circRNAs）是多种人类癌症的关键调节因子，circ-ERBB2在乳腺癌细胞中异常表达。然而，circ-ERBB2在HER2阳性乳腺癌中的作用和机制仍不清楚。
采用定量实时PCR检测HER2阳性乳腺癌患者肿瘤组织中circ-ERBB2的表达。通过细胞计数试剂盒8检测、Transwell实验、流式细胞术和蛋白质免疫印迹法研究circ-ERBB2的功能。机制上，进行荧光原位杂交、RNA免疫沉淀、RNA下拉和双荧光素酶报告基因实验，以证实HER2阳性乳腺癌细胞中circ-ERBB2与miR-136-5p或miR-198之间的相互作用。
circ-ERBB2在HER2阳性乳腺癌患者的肿瘤组织中升高。在功能上，干扰circ-ERBB2可抑制HER2阳性乳腺癌细胞的增殖、迁移、侵袭并加速细胞凋亡。此外，机制分析证实circ-ERBB2作为miR-136-5p或miR-198的竞争性内源性RNA，以减轻miR-136-5p或miR-198对其靶转录因子激活蛋白2C（TFAP2C）的抑制作用。同时，体内实验进一步证实了circ-ERBB2在HER2阳性乳腺癌中的致癌功能。
circ-ERBB2通过circ-ERBB2/miR-136-5p/TFAP2C轴或circ-ERBB2/miR-198/TFAP2C轴加速HER2阳性乳腺癌的进展。
