Circular RNA Circ_0000442 acts as a sponge of MiR-148b-3p to suppress breast cancer via PTEN/PI3K/Akt signaling pathway

Breast cancer remains the most common malignancy in women worldwide. Circular RNAs (circRNAs) are a newly validated type of endogenous non-coding RNAs and accumulating evidence suggests that aberrant circRNAs are involved in disease pathogenesis. However, the function of circRNAs in breast cancer remains largely unknown. This study is aimed to characterize the potential role and mechanism of hsa_circ_0000442 (circ_0000442) in breast cancer. The human breast epithelial cell line (MCF-10A), breast cancer cell lines (MCF-7, T47D, BT474, SK-BR-3, MDA-MB-231, SUM-1315) and the Balb/C Nude mice were used for exploration, and the qRT-PCR, western blot, dual-luciferase reporter assay, glo assay, colony formation assay, and tumor xenograft were carried out for investigation. In this study, the results showed a lower expression of circ_0000442 in breast cancer tumor tissues compared with the adjacent normal tissues. Subsequently, circ_0000442 was found to acted as the sponge of miR-148b-3p in breast cancer cells, thus exerting the tumor-suppressive effects. In the subsequent mechanism study, results showed that miR-148b-3p directly targeted PTEN, a well-known tumor suppressor which negatively regulats PI3K/Akt pathway, thus promoting tumor growth in breast cancer. Overall, this study for the first time identified the tumor-suppressive role of circ_0000442 in breast cancer and found PTEN as a novel direct target of miR-148b-3p. The regulatory role of circ_0000442/miR-148b-3p/PTEN/PI3K/Akt axis was preliminarily confirmed in breast cancer cells and mouse models. These findings suggest an important progress in our standing of breast cancer and lay the foundation for the further function, diagnosis, therapy and prognosis research of circular RNAs in breast cancer.

Automated summary

This study identified the tumor-suppressive role of circ_0000442 in breast cancer for the first time and found PTEN as a novel direct target of miR-148b-3p. The regulatory role of circ_0000442/miR-148b-3p/PTEN/PI3K/Akt axis was preliminarily confirmed in breast cancer cells and mouse models. These findings provide important progress in understanding breast cancer and lay the foundation for further research on the function, diagnosis, therapy, and prognosis of circular RNAs in breast cancer.