Microarray Analysis Reveals Altered Expression Of Multiple Circular RNAs In The Pathogenesis Of Esophageal Squamous Cell Carcinoma

Background Esophageal carcinoma remains one of eighth most prevalent and sixth most fatal malignancies the around the world.Especially in China,where the mobidity of esophageal carcinoma was significantly higher than that of western countries.Esophageal squamous cell carcinoma?ESCC?,as the predominant type in eastern Asia,has its distinct characteristics in risk factor,predilection site,biological behavior and so on.There factors reveals that there are special molecular biological mechanisms within ESCC's pathogenesis.Though the diagnosis and treatment technique has improved greatly,the prognosis of ESCC remains poor,which should be partly attribute to incomplete understanding of specific mechanism of ESCC's pathogenesis.Therefore,new biomarkers act as diagnostic indicator,therapeutic target or prognosis prediction are eagerly expected to be developed to improve the ESCC diagnosis and treatment.Circular RNA?circRNA?is regard as a emerging class of endogenous noncoding RNA characterized by its particular covalently closed-loop molecular structure resulting from a 3'to 5' end joining which was stable and resistant to RNA degradation.CircRNA can function as micro RNA?miRNA?sponge by complementary base pairing with targeted mi RNA using miRNA response elements?MREs?within its molecular structure.In recent years,circRNA has become a hot spot in cancer research for its promising potential as new clinical biomarkers.However,the role of circRNA in the pathogenesis of ESCC is still unclear.We performed this study is aimed to discover circRNAs that took part in ESCC's pathogenesis and evaluate their specific function in order to search of potential biomarkers for ESCC's diagnosis and treatment.Methods The samples were collected from surgical specimens of five ESSC patients and their adjacent non-neoplastic tissues were also collected as control group.All samples were tested by Arraystar Human circRNA Array technology.Differential expressed cirRNAs between groups were identified by bioinformatical analysis,among which 7 circRNA were randomly seleceted for further validation by qRT-PCR.The circRNA/microRNA interaction was predicted with Arraystar's home-made miRNA target prediction software.Result 12,652 circRNAs were detected in tatal.Compared with non-neoplastic tissue,267 circRNAs that were identified significantly differentially expressed in ESCC?fold change > 1.5,P value < 0.05?.Among which,92 circRNAs were up-regulated while 175 were down-regulated,most of differentially expressed circRNAs were composed by exon.5 out of 7 selected circRNAs expression was validated consistent with microarray data by qRT-PCR.Among which,2 circRNAs were up-regulated?hsa_circRNA₁01125,P=0.006;hsa_circRNA₄06826,P=0.004?and 3 circRNAs were down-regulated?hsa_circRNA₁01004,P=0.001;hsa_circRNA₁01839,P=0.019;hsa_circRNA₁03836,P=0.013?.Finally,circRNA/microRNA interaction prediction revealed that 267 differentially expressed circRNAs contain 1332 MREs.Potential targeted miRNAs for 5 selected circRNAs were predicted.They were hsa_circRNA₁01125 and hsa-miR-143-3p,hsa_circRNA₄06826 and hsa-miR-203a-3p,hsa_circRNA₁01004 and hsa-miR-150-5p,hsa_circRNA₁01839 and hsa-miR-143-3p,hsa_circRNA₁03836 and hsa-miR-30a-3p,respectively.Conclusion Our study demonstrates that multiple differential expressed circRNAs are involved in the process of ESCC pathogenesis.And some of these circRNA,for example,hsa_circRNA₁01125 and hsa_circ RNA₄06826 may be considered as new potential biomarks for ESCC diagnosis and treatment.