Down-regulation of long noncoding RNA DLX6-AS1 defines good prognosis and inhibits proliferation and metastasis in human epithelial ovarian cancer cells via Notch signaling pathway

摘要

OBJECTIVE: Long noncoding RNAs (lncRNAs) are key regulatory RNAs which take(s) part in several biological processes. Recently, a newly identified lncRNA, long noncoding RNA DLX6-AS1 (DLX6-AS1), was reported to be involved in the progression of several tumors. However, its expression and biological function in epithelial ovarian cancer (EOC) have not been investigated. The present study aimed to investigate the role of DLX6-AS1 in the development and progression of EOC. PATIENTS AND METHODS: The expression levels of DLX6-AS1 in EOC tissues and cells were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The association between DLX6-AS1 expression and clinicopathologic characteristics and prognosis in patients with EOC was statistically analyzed. Subsequently, loss-of-function assays were performed to explore alterations in a series of cells phenotypes, including cell viability, colony formation, cell cycle, apoptosis, colony formation, and migration and invasion capacities. The effect of DLX6-AS1 on the Notch signaling pathway was evaluated by Western blot and RT-PCR. RESULTS: We first verified the increased expression of DLX6-AS1 in EOC patient samples and cell lines. Clinical assays indicated that high DLX6-AS1 was significantly associated with FIGO stage, lymph node metastasis and poor prognosis. Furthermore, multivariate Cox regression analysis confirmed DLX6-AS1 as an independent prognostic factor in EOC patients. Functionally, the down-regulation of DLX6-AS1 decreased EOC cells proliferation, migration, invasion and induced cell cycle G1/S phase arrest and cell apoptosis. Mechanistic studies revealed that the knockdown of DLX6-AS1 down-regulated Notch1, p21, and Hes1, indicating that the activity of the Notch signaling pathway was inhibited. CONCLUSIONS: Our results demonstrated that DLX6-AS1 inhibited a tumor-promoting role in EOC and may be useful as a prognostic biomarker and/or a therapeutic avenue for EOC.