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Long noncoding RNA DATOC-1 that associate with DICER promotes development in epithelial ovarian cancer by
Wenxing Qin1,2, Yuqing Miao1,3, Guangxia Sun4
1Department of Medical Oncology, Changzheng Hospital, Navy Medical University, Shanghai, China.
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.
Insights
DICER Associated Transcript 1 in Ovarian Cancer (DATOC-1) is a novel lncRNA that promotes epithelial ovarian cancer (EOC) development. Inhibiting DATOC-1 suppresses tumor progression and offers a potential therapeutic target for EOC.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- DICER, a key RNase III enzyme, is downregulated in epithelial ovarian cancer (EOC), correlating with malignancy and poor outcomes.
- This downregulation impacts microRNA maturation, a critical process in cancer development.
Purpose of the Study:
- To identify a long non-coding RNA (lncRNA) that interacts with DICER.
- To investigate the role of this lncRNA in microRNA maturation and EOC progression.
Main Methods:
- RIP-seq to identify DICER-interacting lncRNAs, leading to the discovery of DATOC-1.
- qRT-PCR to analyze DATOC-1 expression in EOC tissues and adjacent samples.
- TCGA data analysis for survival analysis and DATOC-1-based prognostic signatures.
- In vitro and in vivo functional studies using shRNA knockdown and lentiviral transduction.
Main Results:
- DATOC-1 (RP5-1120P11.1) was identified and found to be highly expressed in EOC tissues.
- High DATOC-1 expression correlated with worse prognosis and shorter overall survival (OS) in EOC patients.
- DATOC-1 knockdown inhibited EOC cell proliferation, cell cycle progression, and invasion, suppressing tumor growth in vivo.
- Knockdown of DATOC-1 led to increased miR7 expression, indicating miR7's tumor-suppressive role in EOC.
Conclusions:
- DATOC-1 promotes EOC development by potentially affecting microRNA maturation.
- DATOC-1 serves as a potential biomarker for EOC prognosis.
- DATOC-1 represents a promising therapeutic target for epithelial ovarian cancer.
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