Circular RNA circ-ERBB2 promotes HER2-positive breast cancer progression and metastasis via sponging miR-136-5p and miR-198

• Published in: Journal of translational medicine 2021-11, Vol.19 (1), p.455-455, Article 455
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Apoptosis; Biomarkers; Biotechnology industry; Breast cancer; Breast Neoplasms - genetics; Cell growth; Cell migration; Cell Proliferation; Circ-ERBB2; Circular RNA; Development and progression; ErbB-2 protein; Female; Flow cytometry; Fluorescence in situ hybridization; Gastric cancer; Genetic aspects; Health aspects; HER2-positive breast cancer; Humans; Immunoprecipitation; In Situ Hybridization, Fluorescence; Lung cancer; Medical prognosis; Metastases; Metastasis; MicroRNAs - genetics; miR-136-5p; miR-198; Physiological aspects; Protein 2C; Proteins; Reagents; Receptor, ErbB-2 - genetics; Reporter gene; Ribonucleic acid; RNA; RNA, Circular; TFAP2C; Tumors
• ISSN: 1479-5876; 1479-5876
• 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.