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

Abstract

Esophageal cancer (EC) is one type of aggressive gastrointestinal cancers. The treatment of EC is challenging. Effective therapeutic targets require development. Long non-coding RNA TRPM2 antisense RNA (LncRNA TRPM2-AS) is considering a novel biomarker and therapeutic target for various types of cancer. However, the role of lncRNA TRPM2-AS in EC remains unknown. This study aimed to illustrate effects of LncRNA TRPM2-AS on EC growth and metastasis and potential underlying molecular mechanisms. LncRNA TRPM2-AS expression was determined in both EC tissues and cell lines by quantitative real-time polymerase-chain reaction (qRT-PCR). Cell proliferation ability was evaluated by cell counting kit-8 and colony formation assays. Cell apoptosis was analyzed by flow cytometry. Cell migration and invasion were determined using transwell. Epithelial–mesenchymal transition (EMT)-related markers expression were determined using qRT-PCR and Western blotting. Furthermore, potential lncRNA TRPM2-AS targeting miRNAs were predicted by public databases. The expression of five selected miRNAs were validated by qRT-PCR. We found that lncRNA TRPM2-AS expression was increased in EC tissues and cell lines compared with respective control. Silencing lncRNA TRPM2-AS suppressed EC cell proliferation, migration, and invasion while promoted cell apoptosis. Moreover, lncRNA TRPM2-AS knockdown reduced neural cadherin, vimentin, and matrix metallopeptidase 9 gene and protein expressions while increased epithelial cadherin expression. Furthermore, lncRNA TRPM2-AS knockdown promoted microRNA (miR)-1291, miR-6852-5p, and miR-138-5p expressions. Taken together, this study for the first time demonstrates that upregulation of lncRNA TRPM2-AS in EC promotes the growth and metastasis of EC likely through interacting with miR-1291, miR-6852-5p, and miR-138-5p.

lncRNA TRPM2-AS Promotes Colorectal Cancer Progression by Regulating miR-22-3p and FSTL1

“…Researches on the relationship between differentially expressed lncRNAs and the mechanism of tumorigenesis and development are also being gradually carried out and deepened. TRPM2-AS is a newly discovered noncoding RNA molecule that promotes cancer progression in RB, GC, EC, CRC, and other cancers [ 7 – 10 ]. We found that TRPM2-AS expression was increased in CRC cells and the inhibition of TRPM2-AS hampered CRC cell proliferation, which was consistent with a previous study [ 11 ].…”

“…TRPM2-AS has been reported to have potential diagnostic and prognostic value in many malignancies. Studies have shown that TRPM2-AS can promote the malignant phenotype of ovarian cancer (OC) [ 7 ], retinoblastoma (RB) [ 8 ], gastric cancer (GC) [ 9 ], esophageal cancer (EC) [ 10 ], and other tumor cells and then promote the development of tumors. TRPM2-AS downregulation inhibits progression and interferes with cisplatin resistance in OC [ 7 ].…”

“…In GC, TRPM2-AS promotes the progression by miR-612/IGF2BP1 and radioresistance by FOXM1 [ 9 ]. In EC, tumorigenesis and metastasis are promoted by TRPM2-AS upregulation [ 10 ]. In CRC, TRPM2-AS promotes the proliferation of cells by enhancing TAFL5-mediated TRPM2 mRNA stability [ 11 ].…”

The roles and mechanisms of the lncRNA-miRNA axis in the progression of esophageal cancer: a narrative review

“…Silencing TRPM2-AS by small interfering (si)RNA inhibited the migration and invasion of esophageal cancer cells while promoting expression of miR-1291, miR-6852-5p and miR-138-5p. This suggested that the upregulation of TRPM2-AS promotes invasion and metastasis by interacting with miR-1291, miR-6852-5p and miR-138-5p ( 69 ). The lncRNA TTTY15 acts as a sponge for miR-337-3p to upregulate the expression of JAK2 and promote cell metastasis ( 70 ).…”

The crucial role of long non-coding RNAs in the pathogenesis, therapeutic response, and clinical implications of esophageal cancer

“…Recent studies have highlighted the abnormal expression of lncRNA in the EC and also shown the potential role of them as a therapeutic target in the carcinogenesis process (23,24). In cancer types such as EAC and ESCC, dysregulated lncRNAs may act as potential biomarkers for the diagnosis and prognosis of these types of cancers, as they could participate in therapeutic resistance by regulating cell proliferation, apoptosis, DNA damage repair, and cancer stem cell (CSC) activation (25).…”