Baicalein inhibits breast cancer growth via activating a novel isoform of the long noncoding RNA PAX8‐AS1‐N

Baicalein, a natural flavonoid, has fascinating anti‐cancer properties in breast cancer. Long noncoding RNAs (lncRNAs), a class of transcripts with no protein‐coding potential, also exhibit critical roles in breast cancer. However, the molecular mechanisms mediating the anti‐cancer properties of baicalein and whether lncRNAs are involved in the anti‐cancer effects are still unclear. In this study, we identified a novel isoform of lncRNA PAX8‐AS1 (PAX8‐AS1‐N), which is activated by baicalein in a dose‐ and time‐dependent manner. Functional assays showed that PAX8‐AS1‐N reduced cell viability, inhibited cell‐cycle progression, and induced apoptosis of breast cancer cells in vitro. Depletion of PAX8‐AS1‐N promoted breast xenograft tumor growth in vivo. Furthermore, depletion of PAX8‐AS1‐N attenuated the suppressive roles of baicalein on cell viability, the apoptosis induced by baicalein, and also the suppressive roles of baicalein on tumor growth in vivo. Mechanistically, PAX8‐AS1‐N bound to miR‐17‐5p, and up‐regulated miR‐17‐5p targets, such as PTEN, CDKN1A, and ZBTB4. In addition, PAX8‐AS1‐N was down‐regulated in breast cancer and reduced expression of PAX8‐AS1‐N indicated poor survival of breast cancer patients. In conclusion, our results demonstrated that PAX8‐AS1‐N activation mediated the anti‐cancer effects of baicalein via regulating miR‐17‐5p, and suggested that baicalein and enhancing PAX8‐AS1‐N would be potential therapeutic strategies against breast cancer.