Abstract

BackgroundPrevious 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.MethodsThe 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.ResultsThe 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.ConclusionIn 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.

Highlights

  • Previous genome-wide transcriptome profiling found circ_ZNF124 was highly expressed in lung adenocarcinoma, the role of circ_ZNF124 in non-small cell lung cancer (NSCLC) is still unknown

  • Reporter assay The wild-type circ_ZNF124 or 3′–untrans-lated region (3′–UTR) of Janus Kinase 2 (JAK2) containing the miR-337-3p binding site was cloned into the pGL3–control vector. circ_ZNF124 and JAK2-3′UTR mutants with miR-337-3p binding sites mutation were generated by using Q5 SiteDirected Mutagenesis kit (NEB, USA)

  • Hsa_circ_0017348 derived from ZNF124 was found highly overexpressed in lung adenocarcinoma tumor tissues

Read more

Summary

Introduction

Previous genome-wide transcriptome profiling found circ_ZNF124 was highly expressed in lung adenocarcinoma, 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. Since early stages of lung cancer does not cause any signs and symptoms, the diagnosis is usually made at advanced stages of the disease, the overall 5 year survival rate is pretty low with only around 20% [3, 30]. NSCLC is a subtype of lung cancer with a poor prognosis [12]. 85% of lung cancer cases are NSCLC [2, 27]. Due to the lack of sensitive early diagnosis makers and molecular targets, treatment of NSCLC patients is still not efficient. Exploring the underlying pathogenesis molecular mechanism and identifying novel diagnostic biomarkers are urgent for NSCLC treatment

Objectives
Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call