Hsa_circ_0001615 downregulation inhibits esophageal cancer development through miR-142-5p/ß-catenin.

Background: Recent studies have found that circular RNAs (circRNAs) play important roles in tumorigenesis. This study aimed to determine the function and potential mechanisms of hsa_circ_0001615 in esophageal cancer. Methods: Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the expression of hsa_circ_0001615 and miR-142-5p. Subsequently, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt, flow cytometry, clone formation, and transwell assays were used to assess the function of hsa_circ_0001615. Furthermore, qRT-PCR and Western blot analysis were used to verify cyclin D1, Bcl-2 associated X, B-cell lymphoma/leukemia gene-2, and ß-catenin levels. Circular RNA Interactome was used to estimate the binding site between hsa_circ_0001615 and miR-142-5p. Additionally, dual-luciferase reporter assays were used to determine whether miR-142-5p was a direct target of hsa_circ_0001615. Pearson correlation analysis was used to explore the relationship between miR-142-5p and hsa_circ_0001615. Results: In esophageal cancer, the expressions of hsa_circ_0001615 and miR-142-5p were increased and decreased, respectively. Hsa_circ_0001615 inhibition significantly reduced the proliferation, migration, and invasion but increased the apoptosis of esophageal cancer cells. Additionally, hsa_circ_0001615 knockdown increased miR-142-5p expression but decreased ß-catenin expression. MiR-142-5p was a direct target of hsa_circ_0001615. Conclusion: Hsa_circ_0001615 knockdown could mediate antitumor effects through the miR-142-5p/ß-catenin pathway.

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

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.

Circ0043898 acts as a tumor inhibitor and performs regulatory effect on the inhibition of esophageal carcinoma.

Objective: The study aimed to investigate candidate circular RNAs (circRNAs) in regulating the pathogenic process of esophageal carcinoma. Methods: Specimens were collected from the patients with esophageal carcinoma. Total RNA was purified and treated with RNase R followed by RNA-seq in the purpose of screening the circRNAs in significant differentially expression. The expression level of the screened circRNAs were further validated using RT-PCR. The circular structure of the circRNA was validated with divergent and convergent primers. Overexpression vector was prepared in the purpose of raising the expression level of circ0043898 in the ECA-109 and Kyse-520 cells. The cell colony assay and MTS assay were conducted to determine the capacity of cell proliferation. Chamber assays were applied to determine the capacity of cell migration and invasion while flowcytometry was applied to determine the cell cycle and cell apoptosis. In vivo animal assay was conducted by injecting the cells to the chest of the mice. RNA-seq was performed followed by GO and KEGG study to further verify the regulation mechanism of circ0043898. Results: circ0043898 was validated that down-regulated expressed in the specimens from the patients with esophageal carcinoma. The cell assays proved that overexpression of circ0043898 can obviously inhibit the cell proliferation, cell migration and invasion and induce cell apoptosis and death in the cancerous cells. The in vivo animal study also suggested that the circ0043898 performed inhibitory functions on oncogenesis. The RNA-seq presented the potential regulation mechanism of circ0043898. Histone H3 and BMI1 were presented significantly differential expression in both ECA-109 and Kyse-520 cells, indicating they might be the targets of circ0043898. Conclusion: circ0043898 is presented as tumor inhibitor and could be a candidate biomarker in the therapeutic target and diagnosis of esophageal carcinoma.