<p>Upregulated circ RNA hsa_circ_0000337 promotes cell proliferation, migration, and invasion of esophageal squamous cell carcinoma</p>

Abstract

Background As a new class of endogenous ncRNAs, circRNAs have been recently verified to be involved in the carcinogenesis and progression of human cancers. In the current study, we attempted to explore the potential function of a candidate circRNA (hsa_circ_0000337) in esophageal squamous cell carcinoma (ESCC). Patients and methods The altered expression of hsa_circ_0000337 was validated in clinical samples from 48 patients with ESCC. The human esophageal carcinoma cell lines KYSE-150 and TE-1, and the normal human esophageal epithelial cell line (HET-1A) were applied for functional analysis of hsa_circ_0000337. Cell proliferation was measured using the Cell Counting Kit-8 assay and the colony formation assay. Cell invasion and migration were detected by Transwell and wound healing assays, respectively. We further performed bioinformatic analysis and luciferase reporter assays to explore the role of hsa_circ_0000337 as a miRNA sponge. Results hsa_circ_0000337 was significantly upregulated in ESCC tissues compared to adjacent normal-appearing tissues ( P <0.0001). In our in vitro experiment, the expression of hsa_circ_0000337 was higher in TE-1 compared to the normal human esophageal epithelial cell line HET-1A ( P <0.001), but was not significantly different in KYSE-150 ( P >0.05). Knockdown of hsa_circ_0000337 significantly inhibited cell proliferation, migration, and invasion in TE-1 and KYSE-150 cell lines. Bioinformatics predicted and luciferase reporter assay verified that hsa_circ_0000337 could bind to miR-670-5p, a ncRNA involved in carcinogenesis. It is estimated that 21 genes are regulated by miR-670-5p. Conclusion hsa_circ_0000337 was found to be an upregulated circRNA that is related to ESCC and promotes the progression of disease by regulating cell proliferation, migration, and invasion. These findings suggest that this circRNA could be a promising diagnostic biomarker and potential therapeutic target.

Emerging Role of Non-Coding RNAs in Esophageal Squamous Cell Carcinoma

“…As a novel category of ncRNAs, investigations on the role of circRNAs in ESCC development are still in its initial stages [18,144]. Compared with adjacent non-cancerous tissues, several circRNAs, such as circ-0067934, circ-PRKCI, circRNA-100876, circ-DLG1, and ciRS-7, have been observed to be significantly upregulated in ESCC tissues.…”

“…Identification of aberrant ncRNAs expression in ESCC tissues is of primary importance for studying the function of ncRNAs in ESCC. Quantitative real-time PCR (q-PCR) is a classic method for detecting aberrant ncRNA expression in ESCC tissues [18,52,76]. In recent years, available microarray and next generation sequencing (NGS) techniques bring researchers more complete ncRNA expression profiles between ESCC tumor and normal tissue [5,88,118].…”

“…Overexpression plasmid or small interfering miRNA mimics and inhibitors are commonly used for transient overexpression or knockdown of miRNAs in ESCC cells [34,52,107]. RNA interference (RNAi), mainly involving siRNA and short hairpin RNA (shRNA), has been widely applied in knockdown of ncRNAs in ESCC cells [18,27,31,80]. However, the effectiveness of overexpression plasmid, siRNAs, miRNA mimics, and inhibitors is limited.…”

“…Emerging studies on regulatory ncRNAs have shown their role as biomarkers or physiological regulators in many types of cancers, such as breast cancer, osteosarcoma, lung cancer, hepatocellular carcinoma, cervical cancer, bladder cancer [12][13][14][15][16]. Moreover, there have been increased investigations into the role of ncRNAs in ESCC [17][18][19]. Chen et al revealed that lncRNA FAM201A increases radiosensitivity of ESCC by downregulating miR-101 while upregulating ataxia telangiectasia mutated (ATM) and mammalian target of rapamycin (mTOR) [20].…”

Circular RNA LPAR3 sponges microRNA‐198 to facilitate esophageal cancer migration, invasion, and metastasis

“…The exonic circRNA can serve as the sponge to adsorb miRNAs, so as to finely regulate miRNA‐mediated gene expression 13‐15 . Increasing studies have verified that circRNAs play key roles as tumor suppressor genes or oncogenes in the genesis and development of various cancers, including EC proliferation and progression 16 . Nonetheless, the circRNA expression profiles, function and regulation in ECs remain to be further investigated.…”