Abstract
Background: Ovarian cancer (OC)is a deadly gynecological malignancy worldwide. It is urgent to identify diagnostic biomarkers of OC to disclose the underlying mechanism.Methods and Materials: Bioinformatics analysis was used to identify target genes. Gene expression was detected and altered by qRT-PCR and cell transfection, respectively. The interaction between RP11-499E18.1 and PAK2, as well as that between PAK2 and SOX2, was determined using RNA pulldown, RNA immunoprecipitation (RIP), and co-immunoprecipitation (co-IP) assay, respectively. Localizations of RP11-499E18.1, PAK2, and SOX2 were respectively determined employing immunohistochemical (IHC), IF, and FISH. The regulatory effects of RP11-499E18.1, PAK2, and SOX2 on OC cell proliferation, migration, colony formation, epithelial–mesenchymal transition (EMT)-related factor expression, and SOX2 nuclear translocation were determined. Finally, the effects of RP11-499E18.1 and PAK2 expression on the tumor growth in nude mice were determined.Results: RP11-499E18.1, PAK2, and SOX2 were selected in our study. RP11-499E18.1 was downregulated, while PAK2 and SOX2 was upregulated in OC tissues and cells. RP11-499E18.1 coexists in the nucleus and cytoplasm of OC cells. There is an interaction between RP11-499E18.1 and PAK2, as well as PAK2 and SOX2 in OC cells. Alteration of RP11-499E18.1 and PAK2 expression both had no influence on PAK2 and SOX2 levels, but PAK2 upregulation notably augmented p-SOX2 level. RP11-499E18.1 overexpression suppressed OC cell proliferation, migration, and colony formation, as well as SOX2 nuclear translocation. Besides, it inhibited tumor growth in nude mice. However, these effects were notably reversed by PAK2 upregulation and eventually offset by SOX2 knockdown. Additionally, RP11-499E18.1 overexpression reduced PAK2–SOX2 interaction and SOX phosphorylation, and increased the binding of RP11-499E18.1 by PAK2.Conclusion: These lines of evidence demonstrated that RP11-499E18.1 might play its tumor suppressor roles in OC via regulation of the RP11-499E18.1–PAK2–SOX2 axis. This research indicated that RP11-499E18.1 might be used as a diagnostic biomarker for OC in the future.
Highlights
Ovarian cancer (OC) is one of the most common and deadly gynecological malignancies in the world, which is characterized by high incidence and poor prognosis (Allemani et al, 2018; Kossaï et al, 2018)
An earlier literature demonstrated that Long non-coding RNAs (lncRNAs) participated in the regulation of cellular processes depending on their location: cytoplasmic lncRNAs can affect cellular signaling cascades and regulate mRNA translation or stability, while nuclear lnRNAs are capable of transcriptional regulation, RNA processing, and chromatin interactions (Schmitt and Chang, 2016)
Outcomes showed that the four downregulated lncRNAs, including EGOT, WT1-AS, HAND2AS1, and RP11-499E18.1, exerted typical low expression and poor prognosis, which indicates that these four lncRNAs might be the potential tumor suppressor genes of OC
Summary
Ovarian cancer (OC) is one of the most common and deadly gynecological malignancies in the world, which is characterized by high incidence and poor prognosis (Allemani et al, 2018; Kossaï et al, 2018). Considering that the outcomes of OC patients diagnosed at the early stage of OC is more satisfactory (Cress et al, 2015), identifying new clinical diagnostic biomarkers of OC with high sensitivity and accuracy and thereby obtaining a further understanding of the potential molecular regulating mechanism will be of great significance for future OC treatment. In recent years, accumulating investigations have recorded that it functions as a key regulator in tumor development and progression (Hosono et al, 2017; Bill et al, 2019; Wang et al, 2020). It was disclosed that lncRNAs can exert its regulating roles in various biological functions of tumors, such as proliferation, apoptosis, and metastasis, by post-transcriptional regulation, ceRNA regulation mechanism, genomic stability, and epigenetics (Gutschner and Diederichs, 2012; Arnes et al, 2019; Tang et al, 2019). It is urgent to identify diagnostic biomarkers of OC to disclose the underlying mechanism
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