Multi-omics For Ovarian Cancer Development,apoptosis,Regulation,new Classification Methods And Related Target And Signal Pathway Studies

ObjectiveOur research uses small molecule drugs,non-coding RNA sequences and multi-omics methods to explore the relevant regulatory factors for the development of ovarian cancer,and our data are based on the information of the TCGA database,multi-omics analysis of serous ovarian cancer,to explore the regulation of ovarian cancer Mechanism,apoptosis-related factors,in order to find new targets to improve the clinical diagnosis and treatment of ovarian cancer.Methods1.Inhibition of epithelial ovarian cancer cell lines OVCAR3 and SKOV3 by Arctigenin,pretreatment with ovarian cancer cells by Ac-DEVD-CHO,inhibition of caspase-3 activity.The vector of the empty vector or pcDNA3.1-Survivin was transfected.The cells were intervened using Arctigenin,and the apoptosis was analyzed using a stable and reliable apoptosis detection kit.The binding of immunoreactive complexes was detected by Western blotting and ECL chemiluminescence detection system.2.RT-qPCR was used to detect the expression of DARS-AS1 in ovarian cancer tissue samples.To investigate the effects of DARS-AS1 on proliferation and metastasis of ovarian cancer,explore the underlying mechanisms by luciferase assay and RNA immunoprecipitation.3.DNA of 1203 samples from 599 serous ovarian cancer patients according to public databases.The basicization,protein,microRNA and gene expression were classified by unsupervised classification algorithm,divided into 9 subtypes based on RNA-seq data,and then correlated with prognosis and clinical factors,and based on different omics.The subtype of data integration is assessed for relevance.Results1.High expression of iNOS in ovarian cancer cells in the baseline.Compared with the control group,the expression level of iNOS in the Arctigenin treatment group was 2 to 4 times lower than the baseline.When incubated with chemical NO donors,the inhibition of STAT3 phosphorylation and Survivin expression induced by Arctigenin was reversed;the addition of exogenous NO could antagonize the apoptosis of ovarian cancer cells induced by Arctigenin.2.The expression of DARS-AS1 in ovarian cancer tissues was significantly higher than that in adjacent tissues.When DARS-AS1 is silenced in ovarian cancer cells,cell proliferation is inhibited,and cell migration and invasion ability are also inhibited.microRNA-532-3p is a direct target of DARS-AS1 in ovarian cancer.After knocking down DARS-AS1,miR-532-3p expression was up-regulated.3.(1)Based on the RNA-seq results,the SOC was divided into nine subtypes,and the related genes were mainly aggregated in the following four biological behavior processes:immune activity,hormone metabolism,mesenchymal development,and MAPK signaling(2)Results based on DNA methylation,protein and microRNA expression levels According to differences in methylation,they were divided into four subtypes,which were divided into two clustered NMF models according to the protein array;six groups of highly expressed microRNAs were found based on microRNA expression levels.(3)Four clustered PAM models were determined based on the comprehensive pathway.The results indicate that subtypes based on a omics dataset cannot completely replace data from other omics.Conclusions1.Arctigenin can inhibit the proliferation of ovarian cancer cells.Its mechanism of action is that the drug induces caspase-3-dependent apoptosis in ovarian cancer cells via STAT3/Survivin signaling system;2.DARS-AS1 enhances cell proliferation and metastasis by capturing ovarian cancer miR-532-3p;3.The results of the study indicate that subtypes based on a omics dataset cannot completely replace data from other omics.