Screening And Analysis Of Differentially Expressed Circular RNAs In Breast Cancer And Radioresistant Cells

Increasing studies have shown that circ RNAs plays an important regulatory role in the occurrence,development and radioresistant of cancers,which indicated that circ RNAs may be a novel biomarkers for cancer diagnosis and treatment.Screening the differentially expressed circ RNAs and predicting possible mechanisms in breast cancer tissues and radioresistant cells can provide many candidate molecules and drugs related to development and radioresistance of breast cancer,which is benefitial to early diagnosis and radiosensitivity.Methods: Firstly,screening the differentially expressed circ RNAs in breast cancer tissues from the GEO data,then predicting its functions and related therapeutic drugs.Secondly,establishing the radioresistant cells MCF-7R to screen the differentially expressed circ RNAs by high-throughput sequencing,and sanger sequencing verifying the reverse splicing site and RT-q PCR verifying the expression of candidate circ RNAs and their parental genes in MCF-7R.The target circ RNAs were identified based on the differential expression analysis of circ RNAs and their parental genes.Finally,predicting its functions and possible therapeutic drugs.Results:（1）Through the analysis of two microarray data of breast cancer,97 circ RNAs were differentially expressed in breast cancer tissues.Then 140 mi RNAs and 681 target m RNAs were predicted by the top5 up or down-regulation circ RNAs.GO and KEGG functional analysis concluded that those target m RNAs were closely related to the occurrence and development of breast cancer.In addition,23 candidate drugs with antibreast cancer activity were obtained through DGIdb.Finally,four core genes（CCND1,SMAD4,HIF1 A,CDKN1A）were significantly associated with the prognosis of breast cancer patients.（2）The radioresistant cells MCF-7R were successfully established,and 215 circ RNAs were screened by high-throughput sequencing.The cleavage sites of 9circ RNAs and their expression in MCF-7R are consistent with high-throughput sequencing.According to the difference analysis results,6 circ RNAs（hsa＿circ＿0001946,hsa＿circ＿0002706,hsa＿circ＿0015839,hsa＿circ＿0031446,hsa＿circ＿0085361,hsa＿circ＿0007695）were identified for further verification.（3）100 mi RNAs and 732 target m RNAs were predicted by the 6 circ RNAs.GO and KEGG functions showed that target m RNAs play an important role in tumor metabolism,transcription,gene mutation and radioresistance.Finally,9 candidate drugs to improve breast cancer radiosensitivity were obtained from DGIdb.Conclusion: There are a large number of differentially expressed circ RNAs in breast cancer tissues and radioresistant cells through bioinformatics analysis and highthroughput sequencing.These circ RNAs can participate in the occurrence and development and radioresistance of breast cancer by affecting tumor metabolism,transcription,autophagy,gene mutation etc.These circ RNAs may be the potential biomarkers for early diagnosis and targeted therapy of breast cancer.