Inhibition of gastric cancer cell apoptosis by long noncoding RNA TRPM2-AS via mitogen-activated protein kinase and activators of transduction-3

Abstract

Background and aim: Long noncoding RNA TRPM2-AS has emerged as a novel regulator in cancer initiation and progression of various cancers. However, the function and underlying mechanism of TRPM2-AS in the progression of gastric cancer (GC) remain poorly understood.

Methods: GEO and TCGA databases were used for isolation of differential lncRNA expression. TRPM2-AS expression levels in GC tissues and cells were measured by quantitative polymerase chain reaction method. TRPM2-AS subcellular location was detected by fluorescence in situ hybridization analysis. The functional roles of TRPM2-AS in cells were analyzed by loss and gain function assays.

Results: By using bioinformatics and quantitative polymerase chain reaction methods, TRPM2-AS expression levels were proved to be upregulated in GSE70880 dataset, TCGA database, and 26 GC tissues, which was partly induced by SP1. The results of clinical assays showed that TRPM2-AS could be an indicator for early-stage GC diagnosis. Fluorescence in situ hybridization analysis showed that TRPM2-AS was located in both nucleus and cytoplasm. Functional experiments displayed that knockdown of TRPM2-AS inhibited proliferation, migration, and invasion in GC cells. Furthermore, depression of TRPM2-AS suppressed cell growth though promotion of cell apoptosis. The expression levels of cleaved PARP, caspase 9, caspase 3, and Bax were significantly increased in BGC823 with TRPM2-AS knockdown. In addition, knockdown of TRPM2-AS reduced and phosphorylate signal transducer and activator of transcription 3 and increased and phosphorylate p38 mitogen-activated protein kinase.

Conclusions: This study demonstrated that SP1-regulated TRPM2-AS is involved in GC cell apoptosis probably via p38 mitogen-activated protein kinase and signal transducer and activator of transcription 3 pathways, indicating that TRPM2-AS might be a potential therapeutic target in GC.

Keywords: Apoptosis; Gastric cancer; STAT3; TRPM2-AS; p38.