lncRNA HOTTIP facilitates osteosarcoma cell migration, invasion and epithelial-mesenchymal transition by forming a positive feedback loop with c-Myc

Homeobox A transcript at the distal tip (HOTTIP) is an oncogenic long non-coding RNA in cancer. The aim of the present study was to investigate the function and mechanism of HOTTIP in the aggressive behaviors of human osteosarcoma (OS) cells. Expression levels of HOTTIP and epithelial-mesenchymal transition (EMT) markers were determined by reverse transcription-quantitative PCR. Cell invasive and migratory abilities were evaluated in vitro using Matrigel and wound healing assays, respectively. Knockdown of HOTTIP expression was achieved by small interfering RNA-mediated silencing. Overexpression of c-Myc was accomplished by transfecting cultured cells with a c-Myc overexpression plasmid. HOTTIP was demonstrated to be upregulated in OS tissues and cell lines; knockdown of HOTTIP inhibited OS cell migration, invasion and EMT, and suppressed c-Myc expression. In addition, overexpression of c-Myc increased HOTTIP expression and enhanced OS cell migration and invasion. HOTTIP promoted cell migration and invasion by upregulating c-Myc in OS. The positive feedback loop formed by HOTTIP and c-Myc may contribute to OS progression, and HOTTIP may act as a therapeutic target for OS.