Long noncoding RNA DATOC-1 that associate with DICER promotes development in epithelial ovarian cancer by upregulating miR-7 expression

Background: DICER is a key RNase III enzyme that cleaves processes miRNAs into their mature form. It is remarkably down-regulated in most epithelial ovarian cancer (EOC) and the down-regulation is associated with high grade malignancy as well as poor clinical outcomes. In this study, we aimed to discover a lncRNA interacting with DICER to participate in the process of microRNAs maturation and as a result promoting development of EOC.

Methods: We conducted a RIP-seq aimed at DICER and we obtained its chromosomal location by aligning the sequence in PubMed. And the lncRNA was named DATOC-1 (DICER Associated Transcript 1 in Ovarian Cancer). We tested relative expression of DATOC-1 in 53 EOC and 7 adjacent ovarian samples by qRT-PCR. Then the expression in EOC patients derived from The Cancer Genome Atlas (TCGA) were analysed to identify DATOC-1-based signatures for EOC prognosis with survival analysis. Lastly, shRNA Screening and lentiviral transduction was used to determine the function of DATOC-1 in vitro and in vivo.

Results: We identified the lncRNA RP5-1120P11.1 as DATOC-1, which highly expressed in EOC tissues than in adjacent. And Kaplan-Meier analysis indicated that the patients with EOC that expressed high levels of DATOC-1 had a worse prognosis and shorter disease OS compared with DATOC-1 low-expressed patients. In addition, DATOC-1 were further identified participating in EOC cell proliferation, cell cycle regulation and cell invasion. And knockdown of DATOC-1 inhibits tumor progression in vivo. Furthermore, knockdown of DATOC-1 increased the expression of miR7. The evidence showed that miR7 functioning as a tumor suppressor gene in EOC.

Conclusions: Our research shows that DATOC-1 can inhibit the development of EOC and is a promising therapeutic target.