LncRNA HEIH/miR-4500/IGF2BP1/c-Myc Feedback Loop Accelerates Bladder Cancer Cell Growth and Stemness

Bladder cancer (BCa) is one of the most prevalent malignancies and more common in men. An aberrantly expressed long noncoding RNA (lncRNA) hepatocellular carcinoma up-regulated EZH2-associated lncRNA (HEIH) has been reported to be implicated in the progression of many cancers, but its role in BCa remains little known. Our study intended to uncover whether and how HEIH regulates BCa progression.

Quantitative real-time polymerase chain reaction (RT-qPCR) was adopted to determine HEIH expression in BCa cell lines. Functional experiments were performed to examine the effects of HEIH on BCa cell proliferation, apoptosis, migration, invasion and stemness. Bioinformatics analysis and mechanism experiments were conducted to investigate the regulatory relationship between HEIH and related molecules in BCa.

HEIH expression was observed to be significantly increased in BCa cell lines. HEIH depletion significantly hindered BCa cell proliferation, migration and invasion. Besides, HEIH up-regulated MYC proto-oncogene, and bHLH transcription factor (c-Myc) expression to promote BCa cell stemness. Moreover, HEIH served as a sponge for miR-4500 to modulate insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) expression, thereby stabilizing c-Myc mRNA level.

Our study demonstrated a positive feedback loop of HEIH/miR-4500/IGF2BP1/c-Myc in BCa progression, offering a novel insight into a possible BCa therapy.