Abstract
Circular RNA (circRNA) is an endogenous noncoding RNA. Accumulative investigations have confirmed that circRNAs play a vital role in carcinogenesis and tumor progression. Herein, we examined the expression and mechanism of circ_0072088 in esophageal squamous cell carcinoma (ESCC). As a result, circ_0072088 was significantly overexpressed in ESCC tissues and cells, which was closely associated with tumor size, invasion depth, clinical stage, and lymph node metastasis of esophageal cancer. Nuclear and cytoplasmic separation as well as FISH assays showed that circ_0072088 was mainly localized in the cytoplasm of ESCC cells. RNase R treatment assay revealed that circ_0072088 was steadier than linear ZFR mRNA. circ_0072088 promoted ESCC cell proliferation, migration and invasion in vitro, and cell proliferation in vivo. Mechanistically, circ_0072088 upregulated VEGF gene expression by acting as the sponge of miRNA-377. In conclusion, circ_0072088 might be used as a diagnostic biomarker and therapeutic target for ESCC.
Highlights
Esophageal cancer (EC) is one of the most common malignancies worldwide, ranking the seventh in terms of incidence and the sixth in terms of cancer-related death among the 10 most common malignancies globally [1]
EC is mainly divided into two major pathological categories: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), with ESCC accounting for as high as 90% [2]
By searching and analyzing the circular RNA interactome and starBase databases, we found that nine miRNAs had the binding sites for circ_0072088, including miRNA-223, miRNA-330-3p, miRNA-377, miRNA-532-3p, miRNA-545, miRNA-616, miRNA-1270, miRNA-620, and miRNA-624 (Figure 4(a)). e Quantitative Real-Time PCR (qRT-PCR) assay showed that miRNA-377 expression was significantly upregulated after knocking down circ_0072088 in TE-13 cells, while the expression of other miRNAs was not significantly changed (Figure 4(b))
Summary
Esophageal cancer (EC) is one of the most common malignancies worldwide, ranking the seventh in terms of incidence and the sixth in terms of cancer-related death among the 10 most common malignancies globally [1]. EC is mainly divided into two major pathological categories: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), with ESCC accounting for as high as 90% [2]. Due to a lack of typical symptoms in the early stage in most EC patients, the diagnosis rate in the early stage is low, while the majority of EC patients are already in an advanced stage at diagnosis [3]. Circular RNAs (circRNAs) are a novel type of noncoding RNAs existing in eukaryotes with abundant expression [5]. Unlike linear RNA, circRNAs have a covalently closed loop structure without 5′ to 3′ polarity, making it more resistant to RNase R, which makes circRNA more stable than its linear counterparts in cells [7].
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