LncRNA MACC1-AS1 associates with DDX5 to modulate MACC1 transcription in breast cancer cells

Summary

MACC1 is a master oncogene involved in multiple aspects of cancer metastasis in a broad variety of tumors. However, the molecular mechanism by which MACC1 transcription is regulated remains unclear. Here, we show that in breast cancer cells, lncRNA MACC1-AS1 serves as a cis-factor to up-regulate MACC1 transcription and this regulation increases the cell proliferation potential. Mechanistically, MACC1-AS1 forms a complex with DEAD-Box helicase 5 (DDX5) and simultaneously interacts with the distal region of the MACC1 promoter. The interaction allows its associated DDX5 to spatially contact the MACC1 core promoter and shift from MACC1-AS1 to the core promoter. Moreover, binding of DDX5 to the core promoter results in local recruitment of the transcription factor SP-1, thus enhancing MACC1 transcription. Our findings reveal a molecular mechanism by which MACC1-AS1 cis-regulates MACC1 transcription by interacting with the distal promoter region and delivering DDX5 to the core-promoter of the gene.

Graphical abstract

Highlights

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  MACC1-AS1 complexes with DDX5 and meantime interacts with the MACC1 distal promoter

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  MACC1-AS1 mediates its associated DDX5 to bind to the core promoter of the MACC1 gene

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  Binding of DDX5 to the core promoter recruits SP-1 and activates MACC1 transcription

Abstract

Molecular mechanism of gene regulation; Molecular interaction; Cancer