Long noncoding RNA AOC4P regulates tumor cell proliferation and invasion by epithelial–mesenchymal transition in gastric cancer

Abstract

Background: The clinical relevance and biological role of tissular AOC4P in gastric cancer (GC) remains to be clarified. Methods: The association between AOC4P expression and clinicopathological characteristics was investigated. In vitro , 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, wound healing and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were performed to explore the biological effects of AOC4P on GC cell proliferation, migration, invasion, and apoptosis in MGC-803 and BGC-823 cell lines. In vivo , animal experiments were conducted to confirm the in vitro findings. Quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence were used to investigate the potential mechanisms. Results: Expression levels of AOC4P were significantly higher in tumor tissues than in noncancerous tissues, and patients with high levels of AOC4P had poor overall and disease-free survival. AOC4P expression was correlated with lymphovascular invasion. In vitro , knockdown of AOC4P inhibited tumor cell proliferation, migration, and invasion, and promoted apoptosis of MGC-803 and BGC-823 cells. In vivo , BGC-823 cells transfected with AOC4P siRNA formed smaller and lighter tumors than BGC-823 cells transfected with negative control siRNA in severe combined immunodeficiency mice. Additionally, the si- AOC4P group had less proliferating cells and more apoptotic cells in tumor xenografts compared with the negative control. Mechanistically, knockdown of AOC4P decreased the expression of vimentin and MMP9, while increasing the expression of E-cadherin. Immunofluorescence confirmed the relationship between AOC4P expression and E-cadherin, vimentin, and MMP9 levels in clinical GC specimens. Conclusions: AOC4P promotes tumorigenesis and progression partly through epithelial–mesenchymal transition in GC. Additionally, AOC4P may serve as a prognostic biomarker for clinical decision making.

Long non-coding RNA AOC4P suppresses epithelial ovarian cancer metastasis by regulating epithelial-mesenchymal transition

“…* p < 0.05, ** p < 0.01, and *** p < 0.001 vs. the NC groups poor prognosis in patients with CRC [11]. Evidence also supported that AOC4P regulated tumor cell proliferation and invasion in GC [12]. However, no study has illustrated the involvement of AOC4P in EOC.…”

“…For AOC4P, previous studies have revealed that the overexpression of AOC4P prominently reduced HCC and CRC cell metastasis. However, in GC, AOC4P was upregulated and promoted the migration and invasion of GC cells [10][11][12]. There was previous evidence that the expression levels of lncRNAs varied in various carcinomas with different tumor cell functions.…”

“…Growing evidence has noted that EMT-related lncRNAs play critical roles in the progression of various types of tumours via diverse mechanisms [35]. Previous in mechanistic investigations have indicated that certain EMT regulators participate in AOC4P-mediated anti-metastatic behaviours [10][11][12]. Nonetheless, the molecular events underlying AOC4Pmediated anti-metastatic behavior of EOC are not elucidated.…”

“…The copper containing 4, pseudogene (AOC4P) is a recently discovered EMTrelated lncRNA that was initially reported in hepatocellular carcinoma (HCC) [10]. Evidence has also shown the involvement of AOC4P in colorectal cancer (CRC) and gastric cancer (GC) [11,12]. However, studies regarding the clinical value and biological role of AOC4P in EOC have not been elucidated.…”

Competing Endogenous RNA Networks in the Epithelial to Mesenchymal Transition in Diffuse-Type of Gastric Cancer

“…In this way, AGAP2-AS1 could participate as an epigenetic repressor of E-cadherin expression. As shown in Figure 3 , several other lncRNAs (Lnc01614, LOC554202, TUG1, AFAP1-AS1, NEAT, MNX1-AS1, AOC4P, SNHG20, CCAT1, TPT1-AS1, and LINC00941) have been found to be upregulated and associated with poor prognosis in clinical samples of GC [ 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 ]. The knockdown of these lncRNAs was associated with the re-expression of E-cadherin.…”