A positive feedback loop of long noncoding RNA CCAT2 and FOXM1 promotes hepatocellular carcinoma growth

摘要

Hepatocellular carcinoma (HCC) is one of the most common malignancies around the world. Long noncoding RNAs (lncRNAs) are greater than 200 nucleotides without protein-coding potential and play critical roles in tumorigenesis, cell differentiation, and cancer metastasis. Colon cancer-associated transcript 2 (CCAT2), a newly identified lncRNA, was shown to be dysregulated in cancers. However, the functional role of CCAT2 in HCC remains questionable. In the present study, we found a significant upregulation of CCAT2 in HCC tissues as compared to non-tumor tissues. Functional assays showed that CCAT2 promotes cell growth in vivo and in vitro. In addition, we found a positive feedback loop between CCAT2 and FOXM1. CCAT2 upregulates FOXM1 expression through interaction with, and suppression of, miR-34a, and FOXM1 activates CCAT2 transcription. We evaluated the therapeutic potential of ultrasound-targeted microbubble destruction (UTMD)-mediated siRNA delivery to specifically target CCAT2. UTMD-mediated siCCAT2 delivery significantly suppressed tumor growth in vivo. Thus, CCAT2-FOXM1 may be a novel target for the treatment of HCC.