miRNA-regulated delivery of lincRNA-p21 suppresses β-catenin signaling and tumorigenicity of colorectal cancer stem cells

摘要: Cancer stem cells (CSCs) are key cellular targets for effective cancer therapy, due to their critical roles in progression and chemo/radio-resistance. Emerging evidence demonstrates that long non-coding RNAs (lncRNAs) important players the biology of cancers. However, it remains unknown whether lncRNAs could be exploited target CSCs. We report large intergenic RNA p21 (lincRNA-p21) is a potent suppressor stem-like traits CSCs purified from both primary colorectal (CRC) tissues cell lines. A novel lincRNA-p21-expressing adenoviral vector, which was armed with miRNA responsive element (MRE) miR-451 (Ad-lnc-p21-MRE), generated eliminate CRC Integration MREs into adenovirus efficiently delivered lincRNA-p21 contained low levels miR-451. Moreover, inhibited activity β-catenin signaling, thereby attenuating viability, self-renewal, glycolysis vitro. By limiting dilution serial tumor formation assay, we demonstrated Ad-lnc-p21-MRE significantly suppressed self-renewal potential tumorigenicity nude mice. Importantly, application appeared protect normal liver off-target expression tumor-bearing naive Taken together, these findings suggest may promising therapeutic molecules eradicate tumor-suppressor miRNAs, such as miR-451, ensure specificity CSC-targeting strategies.