Epigenetics is the premise of studying heritable changes in gene expression and function that arise through certain mechanisms that do not involve DNA sequence alterations, including primarily regulatory mechanisms such as DNA methylation, histone modifications, and RNA editing (Portela & Esteller, 2010).As research has progressed, it has been found that epigenetic inheritance plays an important role in the development of a variety of major diseases(Navarro et al., 2014; Sarkargar, Mazaheri, Zare, & Hajihosseini, 2021; Szukiewicz et al., 2021). A number of studies have demonstrated the influence of genetic and epigenetic modifications on tumor initiation and progression in ovarian cancer, endometrial cancer, as well as cervical cancerIn contrast to gene mutations, epigenetics does not act by altering the genomic sequence, but by methylating modifications, histone modifications, miRNA regulation, etc. aberrant methylation, histone modification errors, or miRNA dysregulation are closely associated with tumor cell proliferation, autophagy, apoptosis, cell-cell adhesion, invasion, and metastasis (Herceg & Vaissiere, 2011). therefore, this study aimed to mine the differentially expressed genes in ovarian cancer patients with the help of whole transcriptome sequencing technology and Sanger analysis, in order to explore novel therapeutic targets and diagnostic means.
According to statistics, gene mutations account for up to 1 / 4 of ovarian cancer cases. Currently, BRCA1 and BRCA2 have been found to be susceptibility genes for ovarian cancer (Wu et al., 2017), and additional BRIP1, RAD51C, rad51D and mismatch repair genes also play a role (Suszynska, Ratajska, & Kozlowski, 2020). LncRNA HAND2-AS1 / miR-340-5p / BCL2L11 axis can promote proliferation and apoptosis of ovarian cancer through CeRNA mechanism and affect patient survival prognosis(Chen et al., 2019) .In addition, lncRNA MALAT can reach human umbilical vein endothelial cells in a paracrine manner with the help of exosomes from the serum of ovarian cancer patients to regulate angiogenesis by regulating the expression of angiogenesis related genes (Qiu et al., 2018). Finally, lncRNA LINC00161 / miR-128 / MAPK pathway can promote the development of platinum resistance in ovarian cancer tissues (Xu, Zhou, Wu, Wang, & Lu, 2019).In conclusion, our results demonstrated that aberrant expression of lncRNAs could affect several processes, such as tumor proliferation, invasion, metastasis, epithelial mesenchymal transition, vascularization, and platinum chemoresistance, Regulation of ovarian cancer occurrence and development. Studies on lncRNA mechanism of action in ovarian cancer have mainly focused on the mechanism of epigenetic modification: lncRNAs and miRNAs interact with each other, lncRNAs can act as adsorption sponges for miRNAs, and the changes in their expression can lead to changes in miRNA expression, which in turn causes abnormal expression of mRNAs. In addition, lncRNAs also have an interaction relationship with serum exosomes and so on, so this study through extracting serum exosomes, identifying the differentially expressed genes in ovarian patients, deeply investigating the interrelationships between lncrnas and miRNAs, mRNAs and exosomes, and actively searching for specific serum biological markers in ovarian cancer patients to improve the early diagnosis rate of ovarian cancer.
In this study, we performed whole transcriptome sequencing to discover 117 differentially expressed lncRNAs as well as 513 differentially expressed mRNAs by extracting serum exosomes from ovarian cancer patients, and combined 841 predicted target genes derived from miRcode database and miRNA target gene prediction website to map with each other to obtain 11 potential target genes related to ovarian cancer(FGFR3、BMPR1B、TRIM29、FBN2、PAPPA、CCDC58、IGSF3、FBXO10、GPAM、HOXA10、LHFPL4)Moreover, GO/ KEGG enrichment analysis of the above 11 target genes revealed that the above targets were mainly involved in regulating biological processes such as transmembrane receptor protein kinase activity, structural molecule activity with elasticity, transforming growth factor - activated receptor activity, and GABA receptor binding, and were mainly enriched in signaling pathways regulating stem cell pluripotency, bladder cancer, glycerolipid metabolism, and cancer Hub carbon metabolism, resistance to EGFR tyrosine kinase inhibitors) and other signaling pathways. Finally, survival prognosis analysis of the above targets identified a statistically significant (P < 0.05) survival curve only for the HOXA10 gene, and HOXA10 gene is mainly involved in the DIO3OS-hsa-miR-27a-3p-HOXA10 epigenetic modification signaling axis to affect the occurrence and development of ovarian cancer and the prognosis change of disease survival in this study.
The long noncoding RNA DIO3OS has been implicated in the development and progression of a variety of tumors(Cui et al., 2019; M. Wang et al., 2021; Z. Wang, Song, Ye, & Li, 2020), however, its specific role in the development and progression of ovarian cancer has not been investigated. In addition, hsa-miR-27a-3p has been shown to affect tumor proliferation, invasion, metastasis in glioblastoma, intrahepatic cholangiocarcinoma, and other malignancies(Salmani et al., 2021; Weiyu Xu, 2020) .In parallel, upregulated expression of HOXA10 promotes epithelial mesenchymal transition as well as proliferation, migration and invasion of ovarian cancer cells and decreases patient survival (Jiang et al., 2014; Liu et al., 2018; Nie et al., 2021).Therefore, the target gene HOXA10 may affect the prognosis of patients with ovarian cancer by regulating transcriptional dysregulation pathways in cancer, while affecting processes such as tumor proliferation, invasion, metastasis, epithelial mesenchymal transition, vascularization, and platinum chemoresistance.