Long non-coding RNA TRPM2-AS regulates microRNA miR-138-5p and PLAU (Plasminogen Activator, Urokinase) to promote the progression of gastric adenocarcinoma

Abstract

Gastric adenocarcinoma (GAC) is a common malignant tumor, accounting for 95% of gastric cancers. However, the effects and regulatory mechanisms of long non-coding RNA TRPM2-AS (TRPM2-AS) in GAC have not been fully explored. Our study investigates the action mechanism of TRPM2-AS in GAC. After performing quantitative Real-Time polymerase chain reaction or western blotting, we found that the levels of TRPM2-AS and Plasminogen Activator, Urokinase (PLAU) were upregulated in GAC, whereas the level of miR-138-5p was downregulated. Cell function experiments proved that silencing TRPM2-AS suppressed proliferation and migration and induced apoptosis in GAC cells. Bioinformatic analysis and luciferase assay identified the interaction between TRPM2-AS, miR-138-5p, and PLAU. In addition, the inhibitory effect of silencing TRPM2-AS on GAC cells could be partially relieved by PLAU overexpression. In conclusion, our study revealed that TRPM2-AS sponging miR-138-5p to upregulate PLAU could contribute to GAC progression, which might be useful for identifying biomarkers for GAC therapy. Abbreviation Gastric adenocarcinoma (GAC); Long non-coding RNA (lncRNA); lncRNA TRPM2 antisense RNA (TRPM2-AS); Plasminogen Activator, Urokinase (PLAU); Wild-type (WT); mutant (MUT).

Long non-coding RNA TRPM2 antisense RNA as a potential therapeutic target promotes tumorigenesis and metastasis in esophageal cancer

“…We found that lncRNA TRPM2-AS might target a total of 410 miRNAs predicted by public databases. Among these miRNAs with high scores, five miRNAs, including miR-1291, miR-6852-5p, miR-138-5p, miR-218-5p, and miR-93-3p, were previously shown to participate in cancer pathogenesis [ 26 , 45–48 ]. This study validated that only miR-1291, miR-6852-5p, and miR-138-5p were increased by lncTRPM2-AS knockdown.…”

“…This study validated that only miR-1291, miR-6852-5p, and miR-138-5p were increased by lncTRPM2-AS knockdown. Among these three miRNAs, only miR-138-5p has published evidence that it was directly targeted by lncRNA TRPM2-AS and thus regulating downstream signaling, e.g., PI3K/AKT in non-small cell lung cancer, syndecan 3 (SDC3) in ovarian cancer, and urokinase in gastric adenocarcinoma [ 20 , 21 , 26 ]. MicroRNA-138 expression was associated with chemosensitivity and radiosensitivity of EC treatment [ 49 , 50 ].…”

“…Emerging evidence demonstrates that lncRNA TRPM2-AS is abnormally expressed in different types of cancers and regulates a variety of cancer cell biological process, e.g., cell proliferation, apoptosis, migration, invasion, drug resistances [ 18–30 ]. For example, lncRNA TRPM2-AS expression increased in gastric adenocarcinoma (GAC), and silencing lncRNA TRPM2-AS inhibited GAC cell proliferation and migration, while enhanced cell apoptosis [ 26 ]. A bunch of microRNAs (miRNAs) were shown to interact with lncRNA TRPM2-AS, contributing to the regulative effects of lncRNA TRPM2-AS on cell functions.…”

“…A bunch of microRNAs (miRNAs) were shown to interact with lncRNA TRPM2-AS, contributing to the regulative effects of lncRNA TRPM2-AS on cell functions. In non-small cell lung cancer cells [ 20 ] and GAC cells [ 26 ], lncRNA TRPM2-AS directly bound to miR-138-5p, regulating EGFR and phosphatidyl-inositol 3-kinase/serine-threonine kinase (PI3K/AKT) signaling, and urokinase ( PLAU ) expression, respectively. LncRNA TRRPM2 also targets miR-22-3p, miR-497, and miR-612 in bladder cancer [ 27 ], retinoblastoma [ 23 ], and gastric cancer [ 29 ], respectively.…”

PLAU is associated with cell migration and invasion and is regulated by transcription factor YY1 in cervical cancer

“…Additionally, PLAU is an important modulator of tumorigenesis and progression. PLAU is overexpressed in several tumors, including head and neck squamous cell carcinoma (HNSCC) (7), gastric adenocarcinoma (8) and breast cancers (9). PLAU participates in tumor progression by promoting tumor cell proliferation, cell migration, invasion, and epithelial-mesenchymal transition (10)(11)(12).…”