LncRNA PCGEM1 enhances metastasis and gastric cancer invasion through targeting of miR-129-5p to regulate P4HA2 expression.
Biomarkers, Tumor
/ genetics
Cell Line, Tumor
Cell Movement
/ genetics
Cell Proliferation
/ genetics
Gene Expression Regulation, Neoplastic
/ genetics
Humans
In Situ Hybridization, Fluorescence
MicroRNAs
/ genetics
Neoplasm Invasiveness
/ genetics
Neoplasm Metastasis
Prolyl Hydroxylases
/ genetics
RNA, Long Noncoding
/ genetics
Stomach Neoplasms
/ genetics
Gastric cancer
P4HA2
PCGEM1
ceRNA
miR-129-5p
Journal
Experimental and molecular pathology
ISSN: 1096-0945
Titre abrégé: Exp Mol Pathol
Pays: Netherlands
ID NLM: 0370711
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
17
01
2020
revised:
18
06
2020
accepted:
18
06
2020
pubmed:
6
7
2020
medline:
16
12
2020
entrez:
5
7
2020
Statut:
ppublish
Résumé
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). 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). 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. 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.
Identifiants
pubmed: 32622013
pii: S0014-4800(20)30763-2
doi: 10.1016/j.yexmp.2020.104487
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
MicroRNAs
0
Mirn129 microRNA, human
0
PCGEM1 non-coding RNA, human
0
RNA, Long Noncoding
0
P4HA2 protein, human
EC 1.14.11.-
Prolyl Hydroxylases
EC 1.14.11.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104487Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest No potential conflicts of interest were disclosed.