Molecular Therapy: Nucleic Acids (Dec 2021)
PHF5A promotes colorectal cancerprogression by alternative splicing of TEAD2
- Yue Chang,
- Yulu Zhao,
- Liya Wang,
- Meijuan Wu,
- Chenglong He,
- Mengxi Huang,
- Zengjie Lei,
- Jiahe Yang,
- Siqi Han,
- Bibo Wang,
- Yanyan Chen,
- Chao Liu,
- Hongju Yu,
- Lijun Xue,
- Jian Geng,
- Yanan Chen,
- Tingting Dai,
- Lili Ren,
- Qian Wang,
- Xiaobei Liu,
- Xiaoyuan Chu,
- Cheng Chen
Affiliations
- Yue Chang
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China
- Yulu Zhao
- Department of Medical Oncology, Jinling Hospital, Nanjing Medical University, Nanjing 210002, China
- Liya Wang
- Clinical Medical College, Yangzhou University, Yangzhou 225009, China
- Meijuan Wu
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China
- Chenglong He
- Department of Medical Oncology, Jinling Hospital, First School of Clinical Medicine, Southern Medical University, Nanjing 210002, China
- Mengxi Huang
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China
- Zengjie Lei
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China
- Jiahe Yang
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China
- Siqi Han
- Department of Medical Oncology, Jinling Hospital, First School of Clinical Medicine, Southern Medical University, Nanjing 210002, China
- Bibo Wang
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China
- Yanyan Chen
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China
- Chao Liu
- Clinical Medical College, Yangzhou University, Yangzhou 225009, China
- Hongju Yu
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China
- Lijun Xue
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China
- Jian Geng
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China
- Yanan Chen
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China
- Tingting Dai
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China
- Lili Ren
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China
- Qian Wang
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China
- Xiaobei Liu
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China; Corresponding author: Xiaobei Liu, Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, Jiangsu 210002, China.
- Xiaoyuan Chu
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China; Department of Medical Oncology, Jinling Hospital, Nanjing Medical University, Nanjing 210002, China; Department of Medical Oncology, Jinling Hospital, First School of Clinical Medicine, Southern Medical University, Nanjing 210002, China; Corresponding author: Xiaoyuan Chu, Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, Jiangsu 210002, China.
- Cheng Chen
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China; Department of Medical Oncology, Jinling Hospital, Nanjing Medical University, Nanjing 210002, China; Department of Medical Oncology, Jinling Hospital, First School of Clinical Medicine, Southern Medical University, Nanjing 210002, China; Corresponding author: Cheng Chen, Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, Jiangsu 210002, China.
- Journal volume & issue
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Vol. 26
pp. 1215 – 1227
Abstract
Dysregulated alternative splicing (AS) plays critical roles in driving cancer progression, and the underlying mechanisms remain largely unknown. Here, we demonstrated that PHF5A, a component of U2 small nuclear ribonucleoproteins, was frequently upregulated in colorectal cancer (CRC) samples and associated with poor prognosis. PHF5A promoted proliferation and metastasis of CRC cells in vitro and in vivo. Transcriptomic analysis identified PHF5A-regulated AS targets and pathways. Particularly, PHF5A induced TEAD2 exon 2 inclusion to activate YAP signaling, and interference of TEAD2-L partially reversed the PHF5A-mediated tumor progression. Pharmacological inhibition of PHF5A using pladienolide B had potent antitumor activity. Collectively, these data revealed the oncogenic role of PHF5A in CRC through regulating AS and established PHF5A as potential therapeutic target.
