Expression And Clinical Significance Of CircRNAs In Lung Adenocarcinoma

Background:Circular RNAs(circRNAs)represent a large class of non-coding RNAs(ncRNAs),and have a widespread distribution in eukaryotes.CircRNAs are originated from back-spliced exons,and may compete with the formation of linear RNAs.More and more studies have demonstrated that circRNAs can contribute to gene expressoin,transcription and translation,and are associated with many diseases,including lung adenocarcinoma(LAD).But there are still a large number of cirRNAs that remain unknown in LAD.Thus,our research was aimed to find out more about functions of circRNAs in LAD.Methods:We analysed circRNAs in 3 paired LAD and paracarcinoma tissues by high-throughput sequencing.Many of them are differently expressed in cancerous and adjacent normal tissues.Hsa?circ?0001640 is shown to be down regulated in LAD tissues.We further compared the expression of hsa?circ?0001640 in 90 pairs of LAD and paracarcinoma tissues by quantitative real-time polymerase chain reaction(qRT-PCR).The result was analysed by paired t test.The clinical significance of hsa?circ?0001640 was assessed by independent sample t test and one-way ANOVA.COX logistic regression was also performed to evaluate the association between hsa?circ?0001640 and overall survival(OS)in 3 years after surgical treatment.To further confirm the function of hsa?circ?0001640 in LAD,A549 and H1299 cell lines were chosen to perform the experiment in vitro.Results:The expression of hsa?circ?0001640 is significantly downregulated in LAD tissues.Hsa?circ?0001640 shows a negative correlation with clinical stage and lymph nodes invasion.Lower hsa?circ?0001640 expression also represents a poorer prognosis in 3 years after surgical ablation of lung lobe,including a higher risk of death,as well as recurrence or metastasis in 3 years.According to the analysis by COX logistic regression,hsa?circ?0001640 acts as a protective factor of OS,while clinical stage is a risk factor.In experiment in vitro,the results demonstrated that hsa?circ?0001640 can obviously inhibit proliferation and invasion of A549 and H1299 cells,and more cells remained in G1 phase with upregulation of hsa?circ?0001640.Conclusions:Hsa?circ?0001640 can function as an inhibitor of LAD by keeping cell cycles in G1 phase.Hsa?circ?0001640 is also an indicator of clinical stage,lymph node invasion and prognosis,and can influence overall survival of LAD patients.