A Preliminary Study On The Invation And Metastasis Of Breast Cancer MDA-MB-231 Cells Promoted By Long Non-coding Rna FAM83H-AS1

Objective: Breast cancer is a malignant disease with high genetic heterogeneity.According to the conservative calculation of statistics,the number of new cases of breast cancer in women aged 30 to 50 in China will reach 2.2 million for the first time by 2021,which is almost equivalent to as many as 100 new cases of breast cancer in every 100,000 women,and the mortality rate is also on the rise.Nowadays,the treatment of breast cancer is mainly based on a variety of tumor comprehensive treatment methods,including surgical treatment,laser treatment,endocrine pathology treatment and targeted drug therapy.At present,the results of diagnosis and treatment of breast cancer are still far from its expectation and target due to many social environmental factors.In particular,the treatment of Triple negative breast carcinoma(TNBC)still remains challenge.For the early diagnosis,treatment and prognosis of tumor,it is urgent to find new biomarkers and targets,which are more effective than traditional methods.Since the 20 th century,studies have found that Long non-coding RNA(LncRNA)plays an indispensable role in a variety of malignancies,and many typical LncRNAs with abnormal expression have also been found in breast cancer.LncRNA is mainly transcribed by RNA polymerase ?(Pol ?),a common non-coding RNA from biological sources.Although lncRNA does not encode proteins,it can regulate the development and prognosis of tumors at multiple levels through mechanisms such as chromatin modification,gene silencing and transcriptional activation.FAM83H-AS1 is a novel lncRNA transcribed from chromosome 8q24.3 on the contralateral side of the adjacent FAM83 H gene.Initially,Cabanski CR et al,used RNA-seq data to compare tumor types with lncRNAs corresponding to normal expression levels in 3000 solid tumor types and found that FAM83H-AS1 expression was significantly increased in colon cancer.Subsequently,phasic research have shown that FAM83H-AS1 expression levels are elevated in many cancers,including colorectal cancer,lung cancer,stomach cancer,bladder cancer,and cervical cancer,but the molecular mechanism of its role in tumors remains unclear.In order to clarify the main role of LncRNA FAM83H-AS1 in the process of breast cancer cell development,and preliminarily investigate its molecular mechanism and related signaling pathways in tumors,so as to provide patients with new clinical treatment hotspots and new markers for early recovery,the role and molecular mechanism of long non-coding RNA FAM83H-AS1 in breast cancer were studied.Methods: Firstly,the sequencing data of LncRNAs and their corresponding clinical information of the cancer tissues of breast cancer patients and adjacent tissues were downloaded from the corresponding database.The R language package was used to analyze the difference of LncRNAs data downloaded from TCGA database,and LncRNAs with different expressions in breast cancer tissues and adjacent tissues were screened.Two breast cancer cell lines(MCF-7 and MDA-MB-231),as well as HBL-100 non-malignant breast epithelial cells were obtained and used.The relative levels of FAM83H-AS1 were detected in HBL-100 cells,MCF-7 cells and MDA-MB-231 cells using quantitative real-time PCR.Recombinant FAM83H-AS1-lentivirus,including overexpression of FAM83H-AS1-lentivirus and negative control were transfected to construct stable FAM83-AS1 expression MDA-MB-231 cells.We performed cell proliferation assay,cell cycle and apoptosis assay,wound healing and transwell cell migration and invasion assay to identify the function of FAM-83H-AS1 in MDAMB-231 cells.Moreover,we adopt the transcriptome sequencing between overexpressed FAM83H-AS1 MDA-MB-231 cells and negative control in order to screen the differentially expressed genes.Finally,the downstream target genes were determined by combining with western blot and other experimental methods.Results: LncRNA FAM83H-AS1 was downregulated in MDA-MB-231 cells(triple negative breast cancer cells).Overexpression of FAM83H-AS1 inhibited the proliferation,migration and invasion of MDA-MB-231 breast cancer cells,and downregulated the expression of proto-oncogene c-jun.Conclusion: FAM83H-AS1 may be involved in the progression of triple negative breast cancer,which could provide new therapy target in triple negative breast cancer.