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LincRNA-ROR promotes metastasis and invasion of esophageal squamous cell carcinoma by regulating miR-145/FSCN1

Authors Shang M, Wang X, Zhang Y, Gao Z, Wang T, Liu R

Received 21 November 2017

Accepted for publication 23 December 2017

Published 31 January 2018 Volume 2018:11 Pages 639—649

DOI https://doi.org/10.2147/OTT.S157638

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Dr XuYu Yang


Muhe Shang, Xianghu Wang, Ying Zhang, Zhikui Gao, Tian Wang, Ran Liu

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu, China

Background and objective: In an attempt to discover a new biomarker for early diagnosis and prognosis of esophageal squamous cell carcinoma (ESCC), the regulation mechanism of large intergenic non-coding RNA–regulator of reprogramming (lincRNA-ROR) as a microRNA (miRNA) sponge was studied.
Patients and methods: ROR expression in 91 pairs of ESCC tissue samples and matched adjacent tissues was quantified with real-time fluorescent quantitative polymerase chain reaction (qRT-PCR). The ROR–miRNA–mRNA regulatory network was built with 161 esophageal cancer (EC) tissues and 11 adjacent tumor tissues from The Cancer Genome Atlas (TCGA) database. A total of 96 cases of ESCC from TCGA database were collected for analysis on survival rates. The regulatory relationship between ROR, miR-145 and FSCN1 was verified in ESCC cells via qRT-PCR, dual luciferase reporter (DLR) assay, RNA immunoprecipitation (RIP) and Western blotting. The transwell method was used to detect cell migration and invasion.
Results: ROR expression in ESCC tumor tissues was significantly higher than in the adjacent tissues, p<0.001. The survival rate of ESCC patients with high ROR expression levels was lower than that of patients with low ROR expression levels (p<0.001). ROR overexpression could downregulate miR-145 by up to 50% was proven by RIP, DLR assay, and qRT-PCR. Two effective binding sites of ROR to miR-145 were verified by DLR assay. One of the sites has never been cited in the literature. The Western blotting results showed that FSCN1 was a downstream target of ROR/miR-145 (p<0.05). Transwell assays were used to show that overexpression of ROR enhanced migration and invasion behavior of ESCC and miR-145 hindered these effects.
Conclusion: ROR acted as a competitive endogenous RNA (ceRNA) of miR-145 in ESCC. A novel, effective miR-145 binding site of ROR was discovered. The ROR/miR-145/FSCN1 pathway was shown to take part in the metastasis of ESCC. ROR is likely an oncogene biomarker for ESCC early diagnosis and prognosis.

Keywords: ESCC, lncRNA, ceRNA, ROR, miR-145, FSCN1
 

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