Long non-coding RNA PTPRG-AS1 promotes cell tumorigenicity in epithelial ovarian cancer by decoying microRNA-545-3p and consequently enhancing HDAC4 expression
Authors: Xijian Xu
Hui Yang
Dan Zhang
Xuan Wei
Jiuyan Zhang
Wenqing Luan
Rui Li
Chang Li
Juanjuan Shi
Peishu Liu
Journal: Journal of Ovarian Research (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Anticancer treatments; Non-coding RNA; PTPRG antisense RNA 1; ceRNA.
Affiliations: Department of Gynaecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, 107 West Wenhua Road, Jinan, 277599, Shandong, China., Department of Gynaecology, Tengzhou Center People's Hospital, Zaozhuang, 277500, Shandong, China., Department of Gynaecology, Rizhao Central Hospital, Rizhao, 276800, Shandong, China., Department of TCM Pharmacy, Tengzhou Center People's Hospital, Zaozhuang, 277500, Shandong, China., Department of Clinical Pharmacy, Tengzhou Center People's Hospital, Zaozhuang, 277500, Shandong, China., Department of Pathology, Tengzhou Center People's Hospital, Zaozhuang, 277500, Shandong, China., Department of Gynaecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, 107 West Wenhua Road, Jinan, 277599, Shandong, China. .

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 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. 

Retracted: No

PubPeer comments:
 Two pairs of flow-cytometry plots share most of their points in common, suggesting that they come from the same raw data files (differently gated and filtered). I have adjusted contrast and aspect ratios for ease of comparison.  Here in context: Left-hand panels are from Figs 1F, 3C, 5C, 6C.  Right-hand panels are respectively from Figs 4B, 6C of [Li et al (2019)] .  Two panels of Fig 3C are surprisingly similar. There may be other matching panels.  ,