Circular Non-coding RNA CircSKI As A Potential Therapeutic Target For Non-small Cell Lung Cancer Using Next Generation Sequencing

Background: Lung cancer remains the most common malignant cancer in the world today.Although the rapid development of medical level has made great progress in the diagnosis and treatment of cancer,the five-year survival rate of patients with advanced lung cancer is still at Very low level.The positive symptoms of early lung cancer are very rare,so it is often found late.In recent research,researchers have gradually shifted their focus to the study of transcription products of some genes.The development of second-generation sequencing technology provides sufficient technical support for the study of transcriptomics.Circular non-coding RNAs(circRNAs)are cyclic RNA molecules that are abundant in cells and do not have the function of encoding proteins.Recent studies have found that certain circRNAs can participate in the molecular mechanisms of tumor cell development.However,the role and mechanism of circular RNA in non-small cell lung cancer is still not very clear.This study identified potential target circRNAs by secondgeneration sequencing and explored its possible molecular biological mechanisms.Methods: This study used a second generation sequencing(NGS,next generation sequence)of surgical samples from patients with non-small cell lung cancer on the Illumina platform to obtain differential expression profiles of differentially expressed circular noncoding RNAs,enriched by multiple functions.To determine the biological function of differentially expressed RNA.Later,through WGCNA(weighted gene co-expression network analysis)combined with differential expression profiles,a potential target,circSKI,was discovered.The bioinformatics tools are then used to predict the microRNAs that they may bind.Finally,through the deep learning algorithm xgboost,the possible molecular biological functions were confirmed.Results: In this study,73 circRNAs were differentially expressed by sequencing the second generation,32 of which were up-regulated circRNAs in cancer tissues,and 41 were circRNAs down-regulated in cancer tissues(Fold change ≥ 2,P < 0.05).The ontology genes of circRNA,which are significantly differentially expressed in tissues,can significantly enrich multiple pathways closely related to the development of NSCLC,such as the intercellular junction pathway.WGCNA analysis showed that circSKI has an important effect on NSCLC tumor size.It is predicted by bioinformatics that circSKI may up-regulate the expression of oncogenes such as MAPK9 by absorbing siRNAs such as hsa-miR-1178,hsa-miR-1205,hsa-miR-1229 and hsa-miR-1281,and participate in tumor cell growth,nucleoplasm Regulation and tumor related functions.Conclusion: This study discovered the potential of circSKI as a tumor marker for lung cancer and its possible molecular mechanisms through next generation sequencing.