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

doi:10.1016/j.heliyon.2023.e17386

Aurora kinase A regulates cancer-associated RNA aberrant splicing in breast cancer

Heliyon. 2023 Jun 24;9(7):e17386. doi: 10.1016/j.heliyon.2023.e17386. eCollection 2023 Jul.

Authors

Sisi Li^{1

2}, Yangfan Qi², Jiachuan Yu³, Yuchao Hao², Lingzhi Xu⁴, Xudong Ding⁵, Minghui Zhang⁶, Jingshu Geng¹

Affiliations

¹ Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China.
² Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
³ Department of Anesthesiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
⁴ Department of Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
⁵ Department of Pathology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
⁶ Department of Oncology, Chifeng City Hospital, Chifeng, China.

Abstract

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.

Keywords: Aurora kinase A; Breast cancer; RNA splicing; Splicing factor.