2. Academic Validation
  3. LncRNA CACClnc promotes chemoresistance of colorectal cancer by modulating alternative splicing of RAD51

LncRNA CACClnc promotes chemoresistance of colorectal cancer by modulating alternative splicing of RAD51

  • Oncogene. 2023 Mar 11. doi: 10.1038/s41388-023-02657-y.
Xinyu Zhang # 1,  Dan Ma # 1 2,  Baoqin Xuan # 1,  Debing Shi # 3 4,  Jie He # 5,  Minhao Yu # 6,  Hua Xiong # 1,  Yanru Ma 1,  Chaoqin Shen 1,  Fangfang Guo 1,  Yingying Cao 1,  Yuqing Yan 1,  Ziyun Gao 1,  Tianying Tong 1,  Xiaoqiang Zhu 1,  Jing-Yuan Fang 1,  Haoyan Chen 7,  Jie Hong 8
Affiliations

Affiliations

  • 1 State Key Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • 2 Department of Gastroenterology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 3 Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
  • 4 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
  • 5 Guangzhou Key Laboratory of Digestive Disease, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital and The Second Affiliated Hospital, South China University of Technology School of Medicine, Guangzhou, China.
  • 6 Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • 7 State Key Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. haoyanchen@sjtu.edu.cn.
  • 8 State Key Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. jiehong97@sjtu.edu.cn.
  • # Contributed equally.
PMID: 36906654 DOI: 10.1038/s41388-023-02657-y
Abstract

Long non-coding RNAs (lncRNAs) play important roles in carcinogenesis. However, the effect of lncRNA on chemoresistance and RNA alternative splicing remains largely unknown. In this study, we identified a novel lncRNA, CACClnc, which was upregulated and associated with chemoresistance and poor prognosis in colorectal Cancer (CRC). CACClnc promoted CRC resistance to chemotherapy via promoting DNA repair and enhancing homologous recombination in vitro and in vivo. Mechanistically, CACClnc specifically bound to Y-box binding protein 1 (YB1, a splicing factor) and U2AF65 (a subunit of U2AF splicing factor), promoting the interaction between YB1 and U2AF65, and then modulated alternative splicing (AS) of RAD51 mRNA, and consequently altered CRC Cell Biology. In addition, expression of exosomal CACClnc in peripheral plasma of CRC patients can effectively predict the chemotherapy effect of patients before treatment. Thus, measuring and targeting CACClnc and its associated pathway could yield valuable insight into clinical management and might ameliorate CRC patients' outcomes.

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