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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The RNA sequence data have been deposited in NCBI’s Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) and are accessible through GEO Series accession number GSE158559.
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This work was supported by National Natural Science Foundation (82230016, 82272979, 82073115, 81891901, 82200603); Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support (No.20152512, 20161309); Guangzhou Municipality Bureau of Science and Technology (No.202201020281).
The authors declare no competing interests.
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Zhang, X., Ma, D., Xuan, B. et al. LncRNA CACClnc promotes chemoresistance of colorectal cancer by modulating alternative splicing of RAD51. Oncogene 42, 1374–1391 (2023). https://doi.org/10.1038/s41388-023-02657-y