LncRNA PCGEM1 enhances metastasis and gastric cancer invasion through targeting of miR-129-5p to regulate P4HA2 expression
Authors: Jun Zhang
Zhi-Chao Zheng
Yue Wang
Hai-Yan Piao
Yan Zhao
Shuai Guo
Tao Zhang
Journal: Experimental and Molecular Pathology (2020)
Discipline: CLINICAL MEDICINE
Keywords: Gastric cancer; P4HA2; PCGEM1; ceRNA; miR-129-5p.
Affiliations: Gastric Cancer Department, Liaoning Cancer Hospital & Institute (Cancer Hospital of China Medical University), No. 44 Xiaoheyan Road, Dadong District, Shenyang City, Liaoning Province 110042, China., Medical Oncology Department of Gastrointestinal Cancer, Liaoning Cancer Hospital & Institute (Cancer Hospital of China Medical University), No. 44 Xiaoheyan Road, Dadong District, Shenyang City, Liaoning Province 110042, China., Gastric Cancer Department, Liaoning Cancer Hospital & Institute (Cancer Hospital of China Medical University), No. 44 Xiaoheyan Road, Dadong District, Shenyang City, Liaoning Province 110042, China. Electronic address: .

Abstract:  Aim: Aberrantly expressed long non-coding RNAs (lncRNAs) are critical instigators of gastric cancer (GC) progression and metastasis. The ceRNA (competing endogenous RNAs) network is well-known in modulating tumor pathological and physiological processes. This research aims to determine the more effective molecular mechanisms of lncRNA PCGEM1 (prostate cancer gene expression marker 1). Methods: Bioinformatics database and Ago2-RIP were performed to predict and verify the potential targets of lncRNA PCGEM1. Both gain- and loss-of-function experiments were carried out to dissect the biological functions of RNAs. Fluorescence in situ hybridization, dual-luciferase reporter assays, western blot, and real-time PCR (RT-PCR) experiments were utilized to determine the pathophysiological pathways of competitive endogenous RNAs (ceRNAs). Results: GC cells expressed high levels of cytoplasmic PCGEM1. Loss-of-function experiments displayed that the silencing of PCGEM1 suppressed metastatic and invasive cell qualities. PCGEM1 was also found to have associations with miR-129-5p. Subsequently, luciferase reporter and RIP experiments, together with RT-PCR, verified that PCGEM1 functioned as a ceRNA of P4HA2 (Prolyl 4-Hydroxylase Subunit Alpha 2) via sponging miR-129-5p to up-regulate P4HA2 expression. Finally, the rescue assays determined that P4HA2 overexpression rescued the inhibited cell invasion and metastasis caused by PCGEM1 down-regulation. Conclusion: These findings found that an over-expression of PCGEM1 in GC acts as a miR-129-5p sponge, leading to higher levels of P4HA2. The PCGEM1/miR-129-5p/P4HA2 axis was confirmed to possess a crucial role in GC metastasis and invasion, suggesting its utility as a potential diagnostic and therapeutic biomarker. 

Retracted: No

PubPeer comments:
 Figure 4D and F have a problem. Two different micrographs appears three times, and are presented as something else. The micrographs have been modified. ![file] , 
 There are also re-used micrographs between different papers by the authors. Figure 4F from this paper (BCG-823 u2013 (2nd panel from the left)) and Figure 4E from the LINC00163 inhibit.. paper (BCG-832 2nd panel from the left (24h NC)) are the same. [(http: doi.org 10.1007 s10147-019-01604-w)] ![file] , 
 We also found something wrong with the scrape assay image in Figure 4. At first, we had 5 figures but later changed to 4 figures. Our figures were assembled with Adobe Illustrator, there may have been issues with the update. In addition, we also have negligence in the proofreading process. Currently, we are communicating with the magazine to re-upload the data. ,