Abstract
BackgroundOvarian cancer (OvCa) is one of the most common malignant diseases of the female reproductive system in the world. The majority of OvCa is diagnosed with metastasis in the abdominal cavity. Epithelial-to-mesenchymal transition (EMT) plays a key role in tumor cell metastasis. However, it is still unclear whether long non-coding RNA (lncRNA) is implicated in EMT and influences cell invasion and metastasis in OvCa.ResultsIn this study, using bioinformatcis analysis, we constructed a lncRNA-mediated competing endogenous RNA (ceRNA) network for mesenchymal OvCa and identified lncRNA AP000695.4, which we named pro-transition associated RNA (PTAR). PTAR was significantly up-regulated in the mesenchymal subtype samples compared with the epithelial subtype samples from the TCGA OvCa data sets. In addition, our study showed that PTAR expression was positively correlated with the expression level of ZEB1 in the mesenchymal OvCa samples. Meanwhile, we found that silencing miR-101 promoted cell migration, whereas the overexpression of miR-101 suppressed EMT and cell migration in OvCa cell lines through the regulation of ZEB1. Further analysis showed that enhanced expression of PTAR promoted EMT and metastasis through the regulation of miR-101, whereas silencing PTAR led to the attenuation of TGF-β1-induced tumorigenicity in ovarian cancer cells. Mechanistically, we found that PTAR acted as a ceRNA of miR-101, as forced expression of PTAR reduced the expression and activity of miR-101. More importantly, the knockdown of PTAR reduced tumorigenicity and metastasis in vivo.ConclusionsTaken together, the results from our study highlight a role for the PTAR-miR-101-ZEB1 axis in OvCa, which offers novel strategies for the prevention of metastasis in OvCa.
Highlights
Ovarian cancer (OvCa) is one of the most common malignant diseases of the female reproductive system in the world
The miRNA-mRNA interactions and miRNA-long non-coding RNAs (lncRNAs) interactions were collected from the database at http://www.medsysbio.org/ EMTRegulome, which systematically collects the regulations among transcription factors, miRNA, lncRNA and Epithelial-tomesenchymal transition (EMT) genes and records diverse regulatory motifs involved in the EMT process
Identification of competitive RNA (ceRNA) involved in mesenchymal OvCa T tests were performed to detect differentially expressed (DE) genes, lncRNAs and miRNAs in the integrated mesenchymal (iM) subtype compared with the integrated epithelial (iE) subtype of OvCa
Summary
Ovarian cancer (OvCa) is one of the most common malignant diseases of the female reproductive system in the world. Epithelial-tomesenchymal transition (EMT) plays a key role in tumor cell metastasis. It is still unclear whether long non-coding RNA (lncRNA) is implicated in EMT and influences cell invasion and metastasis in OvCa. Ovarian cancer (OvCa), one of the most common gynecological malignancies in women worldwide [1], has a high incidence and high mortality rate and is especially difficult to discover during the early stages. H19 acts as a molecular sponge for the let-7 family, which are well-characterized tumor suppressors [14,15,16] This decrease in let-7 leads to the increased expression of a let-7 target called LIN28, which eventually promotes breast cancer stem cell maintenance [17]. The role and mechanism of lncRNAs in EMT and their influences on cell invasion and metastasis in OvCa, are still not well understood
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