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Long non-coding RNA PTPRG-AS1 promotes cell tumorigenicity in epithelial ovarian cancer by decoying microRNA-545-3p
Juanjuan Shi1,2, Xijian Xu3, Dan Zhang4
1Department of Gynaecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, 107 West Wenhua Road, Jinan, 277599, Shandong, China.
Background:
Long non-coding RNA PTPRG antisense RNA 1 (PTPRG-AS1) deregulation has been reported in various human malignancies and identified as an important modulator of cancer development. Few reports have focused on the detailed role of PTPRG-AS1 in epithelial ovarian cancer (EOC) and its underlying mechanism. This study aimed to determine the physiological function of PTPRG-AS1 in EOC. A series of experiments were also performed to identify the mechanisms through which PTPRG-AS1 exerts its function in EOC.
Methods:
Reverse transcription-quantitative polymerase chain reaction was used to determine PTPRG-AS1 expression in EOC tissues and cell lines. PTPRG-AS1 was silenced in EOC cells and studied with respect to cell proliferation, apoptosis, migration, and invasion in vitro and tumor growth in vivo. The putative miRNAs that target PTPRG-AS1 were predicted using bioinformatics analysis and further confirmed in luciferase reporter and RNA immunoprecipitation assays.
Results:
Our data verified the upregulation of PTPRG-AS1 in EOC tissues and cell lines. High PTPRG-AS1 expression was associated with shorter overall survival in patients with EOC. Functionally, EOC cell proliferation, migration, invasion in vitro, and tumor growth in vivo were suppressed by PTPRG-AS1 silencing. In contrast, cell apoptosis was promoted by loss of PTPRG-AS1. Regarding the mechanism, PTPRG-AS1 could serve as a competing endogenous RNA in EOC cells by decoying microRNA-545-3p (miR-545-3p), thereby elevating histone deacetylase 4 (HDAC4) expression. Furthermore, rescue experiments revealed that PTPRG-AS1 knockdown-mediated effects on EOC cells were, in part, counteracted by the inhibition of miR-545-3p or restoration of HDAC4.
Conclusions:
PTPRG-AS1 functioned as an oncogenic lncRNA that aggravated the malignancy of EOC through the miR-545-3p/HDAC4 ceRNA network. Thus, targeting the PTPRG-AS1/miR-545-3p/HDAC4 pathway may be a novel strategy for EOC anticancer therapy.
Insights
Long non-coding RNA PTPRG antisense RNA 1 (PTPRG-AS1) promotes epithelial ovarian cancer (EOC) malignancy by acting as an oncogene. Silencing PTPRG-AS1 inhibits EOC progression and tumor growth via the miR-545-3p/HDAC4 pathway.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Long non-coding RNA PTPRG antisense RNA 1 (PTPRG-AS1) is implicated in various cancers.
- Its specific role and mechanism in epithelial ovarian cancer (EOC) require further elucidation.
Purpose of the Study:
- To investigate the function of PTPRG-AS1 in EOC development.
- To identify the molecular mechanisms underlying PTPRG-AS1's role in EOC.
Main Methods:
- PTPRG-AS1 expression was quantified in EOC tissues and cell lines using RT-qPCR.
- Functional assays assessed the impact of PTPRG-AS1 silencing on EOC cell behavior in vitro and tumor growth in vivo.
- Bioinformatics, luciferase reporter, and RNA immunoprecipitation assays identified the PTPRG-AS1/miRNA interaction.
Main Results:
- PTPRG-AS1 was upregulated in EOC and associated with poorer patient survival.
- PTPRG-AS1 silencing suppressed EOC cell proliferation, migration, invasion, and tumor growth, while promoting apoptosis.
- PTPRG-AS1 acts as a competing endogenous RNA (ceRNA) by sponging miR-545-3p, leading to increased HDAC4 expression.
Conclusions:
- PTPRG-AS1 acts as an oncogenic lncRNA in EOC, promoting malignancy through the miR-545-3p/HDAC4 ceRNA network.
- Targeting the PTPRG-AS1/miR-545-3p/HDAC4 axis presents a potential therapeutic strategy for EOC.
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