BACKGROUND: Oral squamous cell carcinoma (OSCC) is a type of oral malignancy. Long non-coding RNAs (lncRNAs) have been shown to be related to the occurrence and development of many cancers. Here, we aimed to study the role and molecular mechanism of lncRNA Homeobox A11 antisense RNA (HOXA11-AS) in OSCC.
METHODS: The expression levels of HOXA11-AS, miR-98-5p and Y box binding protein 2 (
YBX2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8), flow cytometry and transwell assays were utilized to determine the proliferation, apoptosis, migration and invasion of OSCC cells. Western blot (WB) analysis was conducted to measure the levels of apoptosis, epithelial-mesenchymal transition (EMT), proliferation-related proteins and
YBX2 protein. Besides, Dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull down assays were carried out to examine the relationship among HOXA11-AS, miR-98-5p and
YBX2. The mice xenograft models were constructed to further determine the effect of HOXA11-AS on OSCC tumor growth in vivo.
RESULTS: HOXA11-AS was highly expressed in OSCC tissues and cells. Knockdown of HOXA11-AS significantly reduced proliferation, migration, invasion and EMT, while promoted apoptosis of OSCC cells. MiR-98-5p was a target of HOXA11-AS, and its inhibitor could revert the inhibition effect of silenced-HOXA11-AS on the progression of OSCC. Also,
YBX2 was a target of miR-98-5p, and its overexpression could invert the suppression effect of miR-98-5p overexpression on the progression of OSCC.
YBX2 expression was regulated by HOXA11-AS and miR-98-5p. Furthermore, HOXA11-AS silencing could reduce the tumor growth of OSCC in vivo.
CONCLUSIONS: HOXA11-AS plays an active role in the progression of OSCC, and the discovery of HOXA11-AS/miR-98-5p/YBX2 axis provides new therapeutic targets for OSCC.