LncRNA MACC1-AS1 associates with DDX5 to modulate MACC1 transcription in breast cancer cells
Guiyu Zheng,
Yanmei Zhu,
Liqun Xu,
Shaoying Chen,
Xiaona Zhang,
Wei Li,
Weibin Chen,
Yanchun Zhou,
Wei Gu
Affiliations
Guiyu Zheng
Department of Pathophysiology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou, Guangdong Province 515041, China
Yanmei Zhu
Department of Pathophysiology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou, Guangdong Province 515041, China
Liqun Xu
Department of Pathophysiology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou, Guangdong Province 515041, China
Shaoying Chen
Department of Pathophysiology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou, Guangdong Province 515041, China
Xiaona Zhang
Department of Pathophysiology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou, Guangdong Province 515041, China
Wei Li
Department of Pathophysiology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou, Guangdong Province 515041, China
Weibin Chen
Department of Pathophysiology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou, Guangdong Province 515041, China
Yanchun Zhou
Department of Pathophysiology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou, Guangdong Province 515041, China
Wei Gu
Department of Pathophysiology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou, Guangdong Province 515041, China; Corresponding author
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.
