Hsa_circ_0000129 drives tumor growth via sequestering miR‐485‐3p and upregulating SPIN1 in breast cancer

• Published in: Journal of biochemical and molecular toxicology 2023-02, Vol.37 (2), p.e23254-n/a
• Main Authors: Zhou, Yuxin, Wu, Minhua, Wen, Limu, Wu, Weizhu
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Apoptosis; Bioinformatics; Blotting, Western; Breast cancer; Breast Neoplasms - genetics; Cell growth; Cell Line, Tumor; Cell migration; Cell Proliferation; circ_0000129; Circular RNA; Disease Models, Animal; Female; Flow cytometry; Humans; Immunoprecipitation; Mammary Neoplasms, Animal; Mice; MicroRNAs - genetics; miR‐485‐3p; Molecular modelling; Polymerase chain reaction; Regulatory mechanisms (biology); Reverse transcription; Sequestering; SPIN1; Tumors; Xenografts; Xenotransplantation
• ISSN: 1095-6670; 1099-0461
• DOI: 10.1002/jbt.23254

Background Breast cancer (BC) is second cancer frequently occurring worldwide. Circular RNA hsa_circ_0000129 (circ_0000129) exerts a tumor‐promoting effect in BC. Nevertheless, the molecular mechanisms mediated by the upregulation of circ_0000129 during BC progression are not well understood. Methods Forty‐five BC patients were recruited for the research. Changes in circ_0000129 levels were detected with quantitative reverse transcription‐polymerase chain reaction. Cell proliferation, apoptosis, migration, invasion, and angiopoiesis were determined by cell counting, 5‐ethynyl‐2′‐deoxyuridine (EdU), flow cytometry, transwell, and tube formation assays. Protein levels were detected by western blot analysis. The regulatory mechanism of circ_0000129 was predicted by bioinformatics analysis and validated by dual‐luciferase reporter and RNA immunoprecipitation assays. In vivo experiments were carried out to verify the function of circ_0000129. Results Circ_0000129 was overexpressed in BC samples and cell lines. Functionally, circ_0000129 silencing reduced cell proliferation, migration, invasion, and promoted cell apoptosis, as well as induced HUVEC angiopoiesis in vitro. Furthermore, circ_0000129 knockdown decreased BC cell growth in mouse xenograft models. Mechanically, circ_0000129 interacted with miR‐485‐3p to mediate the inhibiting effect of miR‐485‐3p on SPIN1. Silenced miR‐485‐3p expression weakened the inhibiting effect of circ_0000129 knockdown on BC cell malignant behaviors. Also, forced SPIN1 expression weakened miR‐485‐3p upregulation mediated effects on BC cell malignant behaviors. Conclusion Circ_0000129 acted as a miR‐485‐3p sponge molecular to mediate expression, thus promoting BC progression. Highlights 1. Circ_0000129 was singularly increased in BC patients. 2. Circ_0000129 silencing curbed BC cell malignant behaviors. 3. Circ_0000129 regulated SPIN1 expression by sponging miR‐485‐3p.