MicroRNA-21 (miR-21) has been revealed to play a crucial role in regulating the biological behavior, including proliferation, migration, invasion and metastasis in certain cancers. However, its role in esophageal squamous cell carcinoma (ESCC) has yet to be elucidated. Based on the data of GSE13937 downloaded from Gene Expression Omnibus (GEO) database, miR-21 was revealed to be one of the top 20 differentially expressed (DE) miRNAs screened using the Morpheus online tool. RAS p21 protein activator 1 (RASA1) was predicted as the target gene of miR-21 using the predicting software and was combined with miR-21 using the luciferase reporter assay. Its relative expression was significantly decreased, however, miR-21 was increased in the tumor tissues compared to the normal adjacent tissues in patients with ESCC as determined by quantitative polymerase chain reaction (q-PCR). Furthermore, overexpression of miR-21 (mimic) could significantly decrease the gene level of RASA1. Conversely, downregulation of miR-21 (inhibitor) significantly increased the gene level of RASA1, while downregulation of RASA1 (siRASA1) markedly increased the gene expression of miR-21. Notably, the expression of Snail and vimentin were significantly increased by upregulation of miR-21 and downregulation of RASA1. Transwell results revealed that miR-21 and RASA1 regulated proliferation, migration and invasion in ESCC cells. In an in vivo model, miR-21 inhibitor (antagomir) could inhibit tumor growth. In conclusion, miR-21 regulated cell proliferation, migration, invasion and tumor growth of ESCC by directly targeting RASA1, which may have been achieved via regulation of Snail and vimentin. Anti-miR-21 revealed an antitumor effect. Thus, it may be considered as a possible target for ESCC therapy.
Background : Recent studies indicate that noncoding circular RNAs (circRNAs) are involved in the development of esophageal carcinoma. This study aimed to identify circRNAs that are differentially expressed in esophageal carcinoma (EC), which may provide potential biomarkers and therapeutic targets for EC and improve the understanding of its tumorigenesis mechanism. Methods : Ten samples of esophageal carcinoma tissues were sent for circRNA microarray detection. Then the data was subjected to bioimformatic analysis (including circRNA-microRNA (miRNA) coexpression network, Spearman’s correlation test and cancer-related circRNA-miRNA axis analyses). The gene expressions of key circRNAs were detected by real-time- PCR. Results: A total of 102 upregulated and 67 significantly downregulated circRNAs were identified in EC tumors compared to adjacent normal tissue by microarray analysis. One upregulated circRNA (hsa_circRNA_401955) showed the most correlation and was thus regarded as the hub gene by the Spearman correlation test. KEGG pathway enrichment analyses showed that four primary pathways (mRNA surveillance, cytoskeletn actin regulation, spliceosome and the NOD-like receptor signaling pathway) were predicted in the five connected miRNA response elements (MREs) of hub circRNA’ s. Furthermore, cancer-related circRNA-miRNA axis analyses revealed that hsa_circRNA_100375 and its four connected MREs contributed to a cancer-related pathway. The expressions of hsa_circRNA_100375 and hsa_circRNA_401955 were increased significantly in the tumor tissues according to q-PCR. Conclusion: CircRNA dysregulation was involved in the tumorigenesis of EC. The key circRNAs of hsa_circRNA_401955 and hsa_circRNA_100375 may serve as potential biomarkers and therapeutic targets for EC.
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