Long noncoding RNA THOR, a novel target biomolecule, is involved in the progression of colorectal cancer

Abstract

THOR is a long noncoding RNA that is highly conserved and highly expressed in a variety of human tumor cells. A large number of studies show that THOR is deeply involved in the occurrence and development of a variety of cancers. However, the role and potential molecular mechanisms of THOR in the initiation and progression of CRC have not been fully elucidated. Here, we demonstrate that THOR is crucial for the occurrence of CRC; it interacts with IGF2BP1 to regulate the downstream Wnt/β-catenin signaling pathway. To clarify the contribution of THOR in the occurrence and development of CRC, we established THOR-deficient APCMin/+ mice and human colorectal cancer cells (SW480) using CRISPR/Cas9 technology. The results showed that the body weight and survival rate of THOR-deficient APCMin/+ mice increased; hyperlipidemia in elderly mice was alleviated, and changes in intestinal structure were attenuated. THOR knockout inhibited the growth, proliferation, and migration of SW480 cells. Downstream regulator genes, including c-MYC, APC, SOX9, Wnt1, CDH1, Axin1, Axin2, LEF 1, were knocked down with THOR knockout. In summary, our results indicate that THOR knockout inhibits the growth and migration of CRC cells and that THOR is a promising prognostic indicator for CRC patients. Moreover, the THOR-IGF2BP1-Wnt/β-catenin axis may be a potential therapeutic target for CRC, providing new insights into the important role of lncRNAs in cancer.