Dataset Information

RSPO3 is a marker candidate for predicting tumor aggressiveness in ovarian cancer.

ABSTRACT:

Background

Ovarian cancer, a highly aggressive and heterogeneous gynecological malignancy that has long been difficult for physicians to identify and treat, requires more effective and precise molecular targets. R-spondin 3 (RSPO3) is a secreted protein that plays a tumorigenic role in several human cancers. However, the functional contribution and prognostic role of RSPO3 in ovarian cancer remain unclear.

Methods

RSPO3 expression in ovarian cancer tissues was assessed using western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemistry, and its relationships to clinicopathological parameters were investigated using the data of 179 ovarian cancer patients. RSPO3's biological function was evaluated using Cell Counting Kit-8, colony formation, wound healing, and Matrigel transwell assay in RSPO3-knockdown and RSPO3-overexpression ovarian cancer cell lines SKOV3 and OVCAR3. The possible biological processes associated with RSPO3 were identified using functional enrichment analysis based on the transcriptome sequencing data from The Cancer Genome Atlas (TCGA) ovarian cancer cohort and our experimental cells, and further verified using western blotting and immunofluorescence in the ovarian cancer cell model.

Results

The RSPO3 mRNA and protein levels were both upregulated in ovarian cancer tissues. High RSPO3 expression was correlated with lymphovascular space invasion (LVSI), lymph node metastasis, distant metastasis, and advanced tumor stage. Survival analysis showed that RSPO3 is an independent prognostic marker in ovarian cancer. Moreover, in vitro RSPO3 knockdown significantly inhibited the invasion ability of ovarian cancer cells, while overexpression significantly promoted it. Using transcriptome sequencing and pathway validation experiments, we demonstrated for the first time that RSPO3 promotes ovarian cancer invasiveness through activation of the PI3K/AKT pathway and modulation of epithelial-mesenchymal transition (EMT), while the common Wnt/?-catenin signaling pathway was not involved.

Conclusions

RSPO3 plays a definite oncogenic role and promotes tumor aggressiveness in ovarian cancer, which may serve as a potential prognostic marker and therapeutic target for this disease.

SUBMITTER: Gu H

PROVIDER: S-EPMC7723610 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

RSPO3 is a marker candidate for predicting tumor aggressiveness in ovarian cancer.

Gu Haifeng H Tu Hua H Liu Lili L Liu Ting T Liu Zhimin Z Zhang Wei W Liu Jihong J

Annals of translational medicine 20201101 21

<h4>Background</h4>Ovarian cancer, a highly aggressive and heterogeneous gynecological malignancy that has long been difficult for physicians to identify and treat, requires more effective and precise molecular targets. R-spondin 3 (RSPO3) is a secreted protein that plays a tumorigenic role in several human cancers. However, the functional contribution and prognostic role of RSPO3 in ovarian cancer remain unclear.<h4>Methods</h4>RSPO3 expression in ovarian cancer tissues was assessed using weste ...[more]

PMID: 33313096

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Project description:In attempt to discover novel aberrantly hypermethylated genes with putative tumor suppressor function in epithelial ovarian cancer (EOC), we applied expression profiling following pharmacologic inhibition of DNA methylation in EOC cell lines. Among the genes identified, one of particular interest was DOK1, or downstream of tyrosine kinase 1, previously recognized as a candidate tumor suppressor gene (TSG) for leukemia and other human malignancies. Using bisulfite sequencing, we determined that a 5'-non-coding DNA region (located at nt -1158 to -850, upstream of the DOK1 translation start codon) was extensively hypermethylated in primary serous EOC tumors compared with normal ovarian specimens; however, this hypermethylation was not associated with DOK1 suppression. On the contrary, DOK1 was found to be strongly overexpressed in serous EOC tumors as compared to normal tissue and importantly, DOK1 overexpression significantly correlated with improved progression-free survival (PFS) values of serous EOC patients. Ectopic modulation of DOK1 expression in EOC cells and consecutive functional analyses pointed toward association of DOK1 expression with increased EOC cell migration and proliferation, and better sensitivity to cisplatin treatment. Gene expression profiling and consecutive network and pathway analyses were also confirmative for DOK1 association with EOC cell migration and proliferation. These analyses were also indicative for DOK1 protective role in EOC tumorigenesis, linked to DOK1-mediated induction of some tumor suppressor factors and its suppression of pro-metastasis genes. Taken together, our findings are suggestive for a possible tumor suppressor role of DOK1 in EOC; however its implication in enhanced EOC cell migration and proliferation restrain us to conclude that DOK1 represents a true TSG in EOC. Further studies are needed to more completely elucidate the functional implications of DOK1 and other members of the DOK gene family in ovarian tumorigenesis.

Dataset Information

RSPO3 is a marker candidate for predicting tumor aggressiveness in ovarian cancer.

Background

Methods

Results

Conclusions

Publications

RSPO3 is a marker candidate for predicting tumor aggressiveness in ovarian cancer.

Similar Datasets

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