Expression And Regulation Mechanism Of LncRNAs In Breast Cancer Combined With Primary Lung Cancer

Breast cancer combined with primary lung cancer is a most common novel tumor in multiple primary neoplasms with high morbidity and mortality among women.With the development of precision medicine and genetic engineering,more attentions are paid to early diagnosis,treatment and prognosis of breast cancer combined with primary lung cancer.Long non-coding RNAs have been shown to play important regulatory role in tumorigenesis of breast cancer and lung cancer.However,the lncRNA expression in breast cancer combined with primary lung cancer remains unknown,and the mechanism of lncRNA expression and regulation in breast cancer combined with primary lung cancer is not clear.This research may provide the guidance for multiple primary neoplasms diagnosis and treatment.In this study,databases of the Cancer Genome Atlas(TCGA)and the lncRNA profiler invented by library were utilized.11 lncRNAs were differentially expressed in breast cancer,9 candidate lncRNAs were differentially expressed in lung cancer.The results showed that PVT1,SNHG6 and NEAT1 were reversely expressed in breast cancer combined with primary lung cancer compared with primary breast or lung cancer.Analyzed the expression of lncRNA at various levels of clinicopathological feature,we found that PVT1 was significantly downregulated in ER,PR,HER2 and p53 positive patients.In addition,the prognosis of breast cancer combined with lung cancer was positively correlated with second primary lung cancer patients' age.What's more,lncRNAs expression did not have significant relationship with the 5-year survival of patients with breast cancer combined with primary lung cancer.These findings revealed that PVT1,SNHG6,NEAT1 may serve as a prognostic marker for breast cancer combined with primary lung cancer.Furthermore,these lncRNAs are potential molecular indicators in the diagnosis and prognosis of other types of multiple primary carcinomas.In the previous study,lncRNA MALAT1 was most significantly upregulated in breast cancer tissues compared with corresponding adjacent tissues.Therefore,we chose the MALTA1 to study the regulation mechanism at the cellular level.Used bioinformatics software to predict the interaction of miR-339-5p with MALAT1,which had the strongest binding ability,we further predicted BLCAP as a potential target gene of miR-339-5p and verified by dual luciferase reporter assay.RT-qPCR experiments explored the regulation of MALAT1-miR-339-5p-BLCAP in breast cancer.Dual luciferase reporter results showed that MALAT1 can regulate mi R-339-5p,and BLCAP can be targeted by mi R-339-5p further influenced the mRNA expression.The results of RT-qPCR showed that BLCAP was downregulated in MCF7 when respectively transfected MALAT1 or miR-339-5p mimic compared with control group.Similarly the mRNA expression was also down-regulated when cotransfected MALAT1 and miR-339-5p mimic,while this downregulation was decreased relatively.In conclusion,MALAT1 may act as a ceRNA,effectively complete the binding site of miR-339-5p,activating the derepression of core transcription factors BLCAP in transcription and translation.MALAT1-miR-339-5p-BLCAP,as a member of the regulatory network of lncRNA-mi RNA-mRNA,reveal the mode of gene expression regulation among various RNA types in breast cancer,which may provide a new potential strategy for breast cancer or other cancers diagnosis and therapy.