Abstract
Increasing studies have shown that long non-coding RNAs (lncRNAs) are regarded as important regulators in the occurrence and development of colorectal cancer (CRC). Although lncRNA CASC9 has been studied in CRC, the detailed regulatory mechanism of CASC9 in CRC is still unclear. In this study, we found that CASC9 was significantly upregulated in CRC tissues and cell lines compared to normal controls and that aberrant expression was associated with the tumor-node-metastasis (TNM) stage of CRC. Functionally, CASC9 depletion efficiently inhibited the proliferation of CRC cells and induced cell apoptosis in vitro. Mechanistically, CASC9 was mainly enriched in the cytoplasm of CRC cells and interacted directly with miR-576-5p. Downregulation of miR-576-5p reversed the inhibitory effect of CASC9 siRNA on CRC cell progression. Furthermore, AKT3 has been identified as a downstream target of miR-576-5p. Spearman's correlation analysis revealed that AKT3 was negatively correlated with miR-576-5p but positively correlated with CASC9. Downregulation of miR-576-5p restored the effect of CASC9 silencing on AKT3 expression. Therefore, silencing CASC9 could downregulate the expression of AKT3 by reducing the competitive binding of CASC9 to miR-576-5p, thus suppressing CRC cell proliferation and promoting cell apoptosis. In summary, we identified CASC9 as an oncogenic lncRNA in CRC and defined the CASC9/miR-576-5p/AKT3 axis, which might be considered a potential therapeutic target for CRC patients, as a novel molecular mechanism implicated in the proliferation and apoptosis of CRC.