Micropeptide CIP2A-BP encoded by LINC00665 inhibits triple negative breast cancer progression

ABSTRACT: TGF-? signaling pathway plays a key role in breast cancer metastasis. Recent studies suggest that TGF-? regulates tumor progression and invasion not only via transcriptional regulation, but also via translational regulation. Using both bioinformatics and experimental tools, we identified a micropeptide CIP2A-BP encoded by LINC00665, whose translation was downregulated by TGF-? in breast cancer cell lines. Using TNBC cell lines, we showed that TGF-? activated Smad signaling pathway induced the expression of translation inhibitory protein 4E-BP1, which inhibited eukaryote translation initiation factor elF4E, leading to reduced translation of CIP2A-BP from LINC00665. CIP2A-BP directly binds tumor oncogene CIP2A to replace PP2A's B56? subunit, thus releasing PP2A activity, which inhibits PI3K/AKT/NF?B pathway, resulting in decreased expression levels of MMP-2, MMP-9 and Snail. Downregulation of CIP2A-BP in TNBC patients was significantly associated with metastasis and poor overall survival. In the MMTV-PyMT model, either introducing CIP2A-BP gene or direct injection of CIP2A-BP micropeptide significantly reduced lung metastases and improved overall survival. In conclusion, we provide evidence that CIP2A-BP is both a prognostic marker and a novel therapeutic target for TNBC.

SUBMITTER: Mr. Binbin Guo 

PROVIDER: S-SCDT-EMBOJ-2019-102190 | biostudies-other |

REPOSITORIES: biostudies-other