Abstract
Accumulating evidence has shown that long non-coding RNAs (lncRNAs) can be used as biological markers and treatment targets in cancer and play various roles in cancer-related biological processes. However, the lncRNA expression profiles and their roles and action mechanisms in ovarian cancer (OC) are largely unknown. Here, we assessed the lncRNA expression profiles in OC tissues from The Cancer Genome Atlas (TCGA) database, and one upregulated lncRNA, LINC01969, was selected for further study. LINC01969 expression levels in 41 patients were verified using quantitative real-time polymerase chain reaction (qRT-PCR). The in vitro effects of LINC01969 on OC cell migration, invasion, and proliferation were determined by the CCK-8, ethynyl-2-deoxyuridine (EdU), wound healing, and Transwell assays. Epithelial–mesenchymal transition (EMT) was evaluated using qRT-PCR and Western blotting. The molecular mechanisms of LINC01969 in OC were assessed through bioinformatics analysis, RNA-binding protein immunoprecipitation (RIP), dual luciferase reporter gene assays, and a rescue experiment. Finally, in vivo experiments were conducted to evaluate the functions of LINC01969. The results of the current study showed that LINC01969 was dramatically upregulated in OC, and patients with lower LINC01969 expression levels tended to have better overall survival. Further experiments demonstrated that LINC01969 promoted the migration, invasion, and proliferation of OC cells in vitro and sped up tumor growth in vivo. Additionally, LINC01969, which primarily exists in the cytoplasm, boosted LARP1 expression by sponging miR-144-5p and promoted the malignant phenotypes of OC cells. In conclusion, the LINC01969/miR-144-5p/LARP1 axis is a newly identified regulatory signaling pathway involved in OC progression.
Highlights
Ovarian cancer (OC) ranks second among lethal gynecological cancers worldwide (Lheureux et al, 2019)
We found that only LINC01969 was associated with survival in ovarian cancer (OC), and higher LINC01969 expression was associated with lower overall survival of OC patients (Figure 1C)
We found that LINC01969 knockdown greatly slowed tumor growth (Figure 8B), and the LINC01969 knockdown tumors were lighter at the end of the experiment (Figure 8C). quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays showed that LARP1, Vimentin, and Snail expression levels were lower and E-cadherin expression levels were higher in mice with LINC01969-silenced tumors (Figures 8D,E), indicating that LINC01969 knockdown decreased LARP1 expression and OC cell Epithelial–mesenchymal transition (EMT) in vivo
Summary
Ovarian cancer (OC) ranks second among lethal gynecological cancers worldwide (Lheureux et al, 2019). 238,719 women worldwide were newly diagnosed with OC in 2012, and 151,917 died from OC (Iversen et al, 2018). LncRNAs function via diverse mechanisms, including chromatin modification and cell signaling (Satpathy and Chang, 2015). In lung cancer, lncRNA LCAT1 functions as a ceRNA by sponging miR-4715-5p to control RAC1 function (Yang et al, 2019). LncRNA MNX1-AS1 induces lung cancer progression through the miR-527/BRF2 pathway (Liu et al, 2019a). LncRNA AC010789.1 promotes colorectal cancer progression by targeting the microRNA-432-3p/ZEB1 axis and the Wnt/β-catenin signaling pathway (Duan et al, 2020). A study of the BRCA1/2 ceRNA network in OC patients with wild-type BRCA1/2 revealed a novel three-lncRNA signature that could predict both prognosis and chemo-response (Zhang et al, 2020)
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