Aurora kinase A regulates cancer-associated RNA aberrant splicing in breast cancer
Sisi Li,
Yangfan Qi,
Jiachuan Yu,
Yuchao Hao,
Lingzhi Xu,
Xudong Ding,
Minghui Zhang,
Jingshu Geng
Affiliations
Sisi Li
Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China; Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China; Corresponding author. Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China.
Yangfan Qi
Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China
Jiachuan Yu
Department of Anesthesiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
Yuchao Hao
Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China
Lingzhi Xu
Department of Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
Xudong Ding
Department of Pathology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
Minghui Zhang
Department of Oncology, Chifeng City Hospital, Chifeng, China; Corresponding author. Department of Oncology, Chifeng City Hospital, Chifeng, China.
Jingshu Geng
Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China; Corresponding author. Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China.
The contribution of oncogenes to tumor-associated RNA splicing and the relevant molecular mechanisms therein require further elaboration. Here, we show that oncogenic Aurora kinase A (AURKA) promotes breast cancer-related RNA aberrant splicing in a context-dependent manner. AURKA regulated pan-breast cancer-associated RNA splicing events including GOLGA4, RBM4 and UBQLN1. Aberrant splicing of GOLGA4 and RBM4 was closely related to breast cancer development. Mechanistically, AURKA interacted with the splicing factor YBX1 and promoted AURKA-YBX1 complex-mediated GOLGA4 exon inclusion. AURKA binding to the splicing factor hnRNPK promoted AURKA-hnRNPK complex-mediated RBM4 exon skipping. Analysis of clinical data identified an association between the AURKA-YBX1/hnRNPK complex and poor prognosis in breast cancer. Blocking AURKA nuclear translocation with small molecule drugs partially reversed the oncogenic splicing of RBM4 and GOLGA4 in breast cancer cells. In summary, oncogenic AURKA executes its function on modulating breast cancer-related RNA splicing, and nuclear AURKA is distinguished as a hopeful target in the case of treating breast cancer.
