Long Noncoding RNA HEIH Promotes Proliferation, Migration and Invasion of Retinoblastoma Cells Through miR-194-5p/WEE1 Axis

BACKGROUND: Abnormally expressed long noncoding RNA (lncRNA) high expression in hepatocellular carcinoma (HEIH) has been implicated in many types of human cancer, and plays crucial roles in tumor development and progression. However, little is known about its function in retinoblastoma. METHODS: qRT-PCR was used to determine the expression levels of HEIH, miR-194-5p and WEE1 in retinoblastoma tissues and cell lines. The trypan blue exclusion method, colony formation assay, wound-healing assay and transwell invasion assay were performed to evaluate the effects of HEIH, miR-194-5p and WEE1 on cell proliferation, migration and invasion. Bioinformatics analysis, dual-luciferase reporter assay and Western blot were employed to investigate the regulatory relationship among HEIH, miR-194-5p and WEE1. RESULTS: We found that HEIH was up-regulated in retinoblastoma tissues and cell lines. Furthermore, high level of HEIH was associated with TNM stage, optic nerve invasion and choroidal invasion of patients with retinoblastoma. Functional studies showed that HEIH knockdown significantly suppressed retinoblastoma cell proliferation, migration and invasion. Mechanistically, HEIH promoted retinoblastoma progression by serving as a sponge of miR-194-5p to regulate WEE1 expression. CONCLUSION: Our work suggests that HEIH acts as an oncogenic lncRNA to promote retinoblastoma proliferation and metastasis, providing a new insight into the retinoblastoma treatment.