Long non-coding RNA HOTTIP promotes tumor growth and inhibits cell apoptosis in lung cancer

Abstract

Lung cancer is one of the leading causes of cancer-related deaths worldwide. Early diagnosis is the best defense against this threat and is therefore of vital importance. In this study, we investigated the role of long non-coding RNA HOTTIP in the tumor growth of lung cancer. Initially, we found that expression of HOTTIP was significantly elevated in 20 cases of lung cancer. HOTTIP was also differentially expressed in a consecutive of lung cancer cell lines. Furthermore, specific shRNA against HOTTIP was employed to deplete expression of HOTTIP in A549 cells and NCI-H446 cells. After successfully depletion of HOTTIP, cell proliferation and colony formation were significantly inhibited in vitro. Tumor growth in vivo was also suppressed after depletion of HOTTIP in a mouse model of lung cancer. Moreover, depletion of HOTTIP caused cell cycle arrest in G0/G1 phase and induced significant cell apoptosis. Cell cycle regulators Cdc25C, Cyclin B1 and Cyclin D1 were decreased upon depletion of HOTTIP. Pro-apoptotic factor Bad was up-regulated, whereas anti-apoptotic factors Bcl-2 and Bcl-xL were down-regulated after HOTTIP ablation. These data suggest that lncRNA HOTTIP contributes to tumor growth in vivo and in vitro and inhibits cell apoptosis in lung cancer.