The Role Of Hsa＿circ＿0057481/miR-200c/ZEB1 In Laryngeal Cancer

Circular RNA(circRNA)is a kind of RNAs with covalent closed-loop structure,which is highly stable and conservative.As a new member of non-coding RNA(ncRNAs),the function,mechanism and clinical application potential of circRNAs have attracted more and more attentions.Most of the circRNAs is high stable and evolutionarily conservative and their expression is tissue-and development stagespecific.Accumulating studies have shown that circRNAs play an important role in various biological processes of tumorigenesis,including cancer development,invasion,metastasis,apoptosis and angiogenesis.CircRNA may be a new promising biomarker for cancer prevention,and it is of great significance in the diagnosis and clinical treatment of human cancer.By the published results of high throughput microarray,we found that the expression of circRNA hsa＿circ＿0057481 was potentially up-regulated in human laryngeal cancer.However,the exact role of this circRNA in laryngeal cancer is not clear.In this study,we first detected the expression of hsa＿circ＿0057481 in laryngeal cancer tissues by q PCR.The results showed that the expression of hsa＿circ＿0057481 was significantly higher in in laryngeal cancer tissues than that in normal control group(P = 0.0116).Next,we silenced the expression of hsa＿circ＿0057481 by siRNA transfection in HEP-2 and TU212 cell lines.We found that knockdown of hsa＿circ＿0057481 could inhibit the growth of laryngeal cancer cells.Cell cycle analysis showed that hsa＿circ＿0057481 silenced cells were arrested in G0 / G1 phase compared with control.Annexin V / PI double staining showed that hsa＿circ＿0057481 could promote laryngeal cancer cell apoptosis.RNA FISH showed that hsa＿circ＿0057481 was mainly located in the cytoplasm.Functionally,we found that silence of hsa＿circ＿0057481 suppressed cell invasion and migration,while the expression of epithelial marker E-cadherin was up-regulated,and the expression of mesenchymal marker β-Catenin was down-regulated.Results of subcutaneous tumor-injection experiment showed that the knockdown of hsa＿circ＿0057481 inhibited xenograft growth,and immunohistochemical staining showed that the number of Ki67 positive cells in the hsa＿circ＿0057481 silenced tumor tissues were significantly lower than that in normal tissues.Furthermore,we found that hsa＿circ＿0057481 complementally bound to miR-200 c to form a ce RNA and modulated the expression of ZEB1.Rescue experiments showed that miR-200 c plays a key role in the function of hsa＿circ＿0057481.In summary,our findings indicate that hsa＿circ＿0057481 plays an important role in the occurrence and development of laryngeal cancer,and can be used as a new target for the diagnosis and treatment of laryngeal cancer.