Long Non-coding RNA PTPRG-AS1 Promotes Cell Tumorigenicity in Epithelial Ovarian Cancer by Decoying microRNA-545-3p and Consequently Enhancing HDAC4 Expression

Abstract

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 done 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, 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. For the mechanism part, 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.

Long non-coding RNA CASC9 promotes tumor progression in oral squamous cell carcinoma by regulating microRNA-545-3p/laminin subunit gamma 2

“…However, we revealed that lncRNA CASC9 regulates the progression of OSCC cells by sponging miR-545-3p to upregulate LAMC2, a mechanism different from that reported by Yang et al Therefore, the regulatory mechanism of lncRNA CASC9 in OSCC has expanded. miR-545-3p, a member of the miRNA family, has been proven to be a tumor suppressor in multiple cancers, such as lung cancer and ovarian cancer [21,23]. Specifically, in a previous report, miR-545-3p sponged by lncRNA PTPRG-AS1 to target histone deacetylase 4 suppressed cell migration and invasion in epithelial ovarian cancer [23].…”

“…miR-545-3p, a member of the miRNA family, has been proven to be a tumor suppressor in multiple cancers, such as lung cancer and ovarian cancer [21,23]. Specifically, in a previous report, miR-545-3p sponged by lncRNA PTPRG-AS1 to target histone deacetylase 4 suppressed cell migration and invasion in epithelial ovarian cancer [23]. However, the function of miR-545-3p in OSCC has not yet been investigated.…”

“…miR-545-3p, a member of the miRNA family, exerts an inhibitory function in multiple cancers [20][21][22]. For example, miR-545-3p, sponged by lncRNA PTPRG-AS1, inhibits cell tumorigenicity in ovarian cancer by attacking its target gene, HDAC4 [23]. However, the function of miR-545-3p in OSCC has not been investigated.…”

The Circ_0001367/miR-545-3p/LUZP1 Axis Regulates Cell Proliferation, Migration and Invasion in Glioma Cells

“…MiR-545-3p dysregulation has been reported in diverse cancers. Shi et al reported that miR-545-3p was downregulated in epithelial ovarian cancer (35); Hao et al showed that miR-545-3p inhibits the proliferation and differentiation of osteoblasts (36); and Zhong et al reported that miR-545-3p functions as a tumor suppressor in endometrial carcinoma (37). Furthermore, some studies indicate that miR-545-3p may be the target of circRNAs.…”

LncRNA PCAT6 promotes proliferation, migration, invasion, and epithelial-mesenchymal transition of lung adenocarcinoma cell by targeting miR-545-3p

“…Significant evidence shows that abnormal regulation of miRNAs is related to the malignant progression of many cancers, and miRNAs are potential therapeutic targets for lung cancer [17]. For example, miR-545-3p has been studied in a variety of cancers including endometrial [18] and ovarian cancer [19]. Another study showed that miR-545-3p was expressed at low levels within NSCLC tumor and cultured cells [20].…”