The most common type of ovarian cancer was epithelial ovarian cancer (EOC). The cause of ovarian cancer was very complicated, which may be caused by factors such as family inheritance, obesity, low immunity, environmental pollution, unreasonable diet, chronic inflammatory stimulation, and benign ovarian cancer [21–27]. Nowadays, with the development of medical treatment, there were many treatments of ovarian cancer [28, 29]. For example, neoadjuvant chemotherapy (NACT) has significantly reduced mortality in the treatment of advanced EOC after diagnosis [30]. In addition, the rise of targeted therapy [31] and immunotherapy also brings more hope to EOC [32]. However, EOC is a highly fatal malignant tumor and is usually diagnosed only at an advanced stage, which will lose the best treatment time [33]. Early diagnosis of EOC has always been a major challenge. Therefore, it is a great significance that searching for specific targets and biomarkers for diagnosis and prognosis of EOC.
LncRNA is considered as the main component of the ceRNA networks, because it regulates the expression of mRNA by absorbing miRNA as a sponge [34, 35]. Therefore, lncRNA obtained increased attention in human cancers as its multifarious function [36–38]. Previous researches showed that lncRNAs played a critical role in the progression of many cancers. For instance, lncRNAs have been studied in lung cancer [39], liver cancer [40], bladder cancer [41], prostate cancer [42] and breast cancer [43]. LncRNAs have also been studied in ovarian cancer, but it is little known about the crosstalk between mRNAs, miRNAs, and lncRNAs, looking for key lncRNAs and exploring the molecular mechanisms related to EOC are an urgent work. In our study, the expression levels and prognosis of lncRNAs in ceRNA network were analyzed through the database GEPIA and Kaplan-Meier plotter, and it was confirmed that LINC01503 was differentially expressed in normal tissues and EOC, and high expression of LINC01503 had an adverse effect on prognosis. In addition, the RT-qPCR experiment further verified our analysis results.
CeRNA network plays an important role to discover biomarkers for clinical prognosis and diagnosis in cancer [44, 45]. Studies have revealed that the activation of the STARD13-correlated ceRNA network is negatively correlated with breast cancer YAP/TAZ activity [46]. In our research, we obtained mRNAs, lncRNAs and miRNAs expression profiles from the GEO database. Next, we constructed ceRNA network of differentially expressed lncRNA-miRNA-mRNA to explore key lncRNAs associated with EOC diagnosis and prognosis. Then it was found that LINC01503 affected the OS and prognosis of EOC patients. Subsequently, we explore the molecular mechanism of LINC01503 through the GO enrichment analyzed the competitive mRNAs of LINC01503. In the 10 biological processes enriched, which response to endoplasmic reticulum stress and IRE1-mediated unfolded protein response have been reported to be related to the occurrence of cancer. Interaction between ER stress contributes to the occurrence and development of various types of cancer[47] Zhang et. al indicated that Angiotensin II promotes ovarian cancer spheroid formation and metastasis by upregulation of lipid desaturation and suppression of ER stress[48]. As the tumor microenvironment is affected by oxidative stress, when the balance between endoplasmic reticulum folding and the degradation of transfer proteins and misfolded proteins is broken, the endoplasmic reticulum (ER) stress response occurs [49]. PERK attenuates IRE1 via RPAP2 to abort failed ER-stress adaptation and trigger apoptosis [50].
The LINC01503 have been reported as an oncogene in non-small cell lung cancer[51], Gastric Cardia Adenocarcinoma[52], cervical cancer[53], etc. We verified that the LINC01503 promote r cell proliferation, migration and inhibited cell apoptosis in ovarian cancer. In the next step, we verified its underlying mechanism. The CTBP-1 is well-known transcriptional corepressors of oncogenic processes [20]. There are some researches revealed the important role of CTBP-1 in EOC before. For example, Ding et al reported that CTBP determines ovarian cancer cell fate through repression of death receptors[54]. He et al. indicated that CtBP-1 differentially regulate genomic stability and DNA repair pathway in high-grade serous ovarian cancer cell[55]. It was the first time to report the regulation role of CTBP1 on LINC01503 in EOC, which was provided the molecular mechanisms for further investigation.