LncRNA CACClnc Promotes Chemoresistance of Colorectal Cancer by Modulating Alternative Splicing of RAD51

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2023 Mar 11

PMID 36906654

Authors

Xinyu Zhang

Dan Ma

Baoqin Xuan

Debing Shi

Jie He

Minhao Yu

Hua Xiong

Yanru Ma

Chaoqin Shen

Fangfang Guo

Yingying Cao

Yuqing Yan

Ziyun Gao

Tianying Tong

Xiaoqiang Zhu

Jing-Yuan Fang

Haoyan Chen

Jie Hong

Affiliations

Soon will be listed here.

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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