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

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.

Automated summary

In this study, a novel upregulated long non-coding RNA (lncRNA) called CACClnc was identified, which was associated with chemoresistance and poor prognosis in colorectal cancer (CRC). The study revealed that CACClnc promoted CRC resistance to chemotherapy by enhancing DNA repair and homologous recombination. The expression of exosomal CACClnc in peripheral plasma of CRC patients was also found to effectively predict the chemotherapy effect prior to treatment. Therefore, targeting CACClnc and its associated pathway could provide valuable insight into clinical management and potentially improve outcomes for CRC patients.