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Cancer Cell International
Published in: Cancer Cell International 1/2019

Open Access 01-12-2019 | NSCLC | Primary research

Circ_ZNF124 promotes non-small cell lung cancer progression by abolishing miR-337-3p mediated downregulation of JAK2/STAT3 signaling pathway

Authors: Qianping Li, Qin Huang, Shaofei Cheng, Song Wu, Hongyang Sang, Junyi Hou

Published in: Cancer Cell International | Issue 1/2019

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Abstract

Background

Previous genome-wide transcriptome profiling found circ_ZNF124 was highly expressed in lung adenocarcinoma, however, the role of circ_ZNF124 in non-small cell lung cancer (NSCLC) is still unknown. The purpose of this study was to investigate the role and molecular mechanism of circ_ZNF124 in NSCLC development.

Methods

The expression of circ_ZNF124, miR-337-3p and JAK2 (Janus Kinase 2) in lung cancer cell lines and normal epithelial cells were detected by qRT-PCR (quantitative real-time PCR). siRNA was used to knockdown circ_ZNF124 expression in cells. The effects of circ_ZNF124 in NSCLC cells were determined by cell growth, cell migration, cell cycle analysis and colony formation. Bioinformatics analysis, RNA immunoprecipitation, luciferase assay and western blots were used to study the molecular mechanism of circ_ZNF124 in NSCLC.

Results

The results showed that circ_ZNF124 expression was highly upregulated in NSCLC cells than in normal epithelial cells. Knockdown of circ_ZNF124 by using siRNA significantly decreased cell growth, promoted cell cycle arrested in sub-G1 phase, impaired cell migration and colony formation. Bioinformatic analysis discovered that miR-337-3p was a direct target of circ_ZNF124. In contrast to circ_ZNF124, miR-337-3p expression was significantly downregulated in NSCLC cells. Biotin labeled circ_ZNF124 immunoprecipitation and luciferase assay showed that miR-337-3p could directly bind to and affect circ_ZNF124 activity. The regulation of circ_ZNF124 on miR-337-3p was also investigated. Further analysis showed that despite STAT3 (signal transducer and activator of transcription 3), JAK2 was also a target of miR-337-3p, overexpression of miR-337-3p greatly downregulated JAK2, STAT3 and JAK2/STAT3 downstream regulated oncogenes HIF1a (Hypoxia-inducible factor 1-alpha), BCL2 (B cell lymphoma 2) and c-FOS expression, however, the roles of miR-337-3p in JAK2/STAT3 signaling pathway were greatly inhibited in the presence of circ_ZNF124.

Conclusion

In NSCLC, highly expressed circ_ZNF124 promoted the activation of JAK2/STAT3 signaling pathway by acting as a sponge of miR-337-3p, thus promoting the occurrence and development of NSCLC. Circ_ZNF124 could be a potential biomarker or target for the treatment of NSCLC patients in the future.
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Metadata
Title
Circ_ZNF124 promotes non-small cell lung cancer progression by abolishing miR-337-3p mediated downregulation of JAK2/STAT3 signaling pathway
Authors
Qianping Li
Qin Huang
Shaofei Cheng
Song Wu
Hongyang Sang
Junyi Hou
Publication date
01-12-2019
Publisher
BioMed Central
Keywords
NSCLC
NSCLC
Published in
Cancer Cell International / Issue 1/2019
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-019-1011-y

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