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Upregulated circ RNA hsa_circ_0000337 promotes cell proliferation, migration, and invasion of esophageal squamous cell carcinoma

Authors Song H, Xu D, Shi P, He B, Li Z, Ji Y, Agbeko CK, Wang J

Received 22 November 2018

Accepted for publication 31 January 2019

Published 4 March 2019 Volume 2019:11 Pages 1997—2006

DOI https://doi.org/10.2147/CMAR.S195546

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Antonella D'Anneo


Huan Song,1,* Dian Xu,1,* Peiyi Shi,1 Biyu He,1 Zhongqi Li,1 Ye Ji,1 Charles Kwaku Agbeko,1 Jianming Wang1,2

1Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, People’s Republic of China; 2Key Laboratory of Infectious Diseases, School of Public Health, Nanjing Medical University, Nanjing 211166, People’s Republic of China

*These authors contributed equally to this work

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.

Keywords: esophageal squamous cell carcinoma, RNA, untranslated RNA, small untranslated, biomarker

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