Journal of Zhejiang University-SCIENCE B

RAD51B-AS1 promotes the malignant biological behavior of ovarian cancer through upregulation of RAD51B

Abstract Long non-coding RNAs (lncRNAs) play an indispensable role in the occurrence and development of ovarian cancer (OC). However, the potential involvement of lncRNAs in the progression of OC is largely unknown. To investigate the detailed roles and mechanisms of RAD51 homolog B-antisense 1 ( RAD51B-AS1 ), a novel lncRNA in OC, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to verify the expression of RAD51B-AS1 . Cellular proliferation, metastasis, and apoptosis were detected using the cell counting kit-8 (CCK-8), colony-formation, transwell, and flow cytometry assays. Mouse xenograft models were established for the detection of tumorigenesis. The results revealed that RAD51B-AS1 was significantly upregulated in a highly metastatic human OC cell line and OC tissues. RAD51B-AS1 significantly increased the proliferation and metastasis of OC cells and enhanced their resistance to anoikis. Biogenetics prediction analysis revealed that the only target gene of RAD51B-AS1 was RAD51B . Subsequent gene function experiments revealed that RAD51B exerts the same biological effects as RAD51B-AS1 . Rescue experiments demonstrated that the malignant biological behaviors promoted by RAD51B-AS1 overexpression were partially or completely reversed by RAD51B silencing in vitro and in vivo. Thus, RAD51B-AS1 promotes the malignant biological behaviors of OC and activates the protein kinase B (Akt)/B cell lymphoma protein-2 (Bcl-2) signaling pathway, and these effects may be associated with the positive regulation of RAD51B expression. RAD51B-AS1 is expected to serve as a novel molecular biomarker for the diagnosis and prediction of poor prognosis in OC, and as a potential therapeutic target for disease management.

Chemerin promotes proliferation and migration of ovarian cancer cells by upregulating expression of PD-L1

Ovarian cancer is the third-most-common malignant reproductive tumor in women. According to the American Cancer Society, it has the highest mortality rate of gynecological tumors. The five-year survival rate was only 29% during the period from 1975 to 2008 (Reid et al., 2017). In recent decades, the five-year survival rate of ovarian cancer has remained around 30% despite continuous improvements in surgery, chemotherapy, radiotherapy, and other therapeutic methods. However, because of the particularity of the volume and location of ovarian tissue, the early symptoms of ovarian cancer are hidden, and there is a lack of highly sensitive and specific screening methods. Most patients have advanced metastasis, including abdominal metastasis, when they are diagnosed (Reid et al., 2017). Therefore, exploring the mechanism of ovarian cancer metastasis and finding early preventive measures are key to improving the survival rate and reducing mortality caused by ovarian cancer.

Single-cell transcriptomics reveals tumor landscape in ovarian carcinosarcoma

The present study used single-cell RNA sequencing (scRNA-seq) to characterize the cellular composition of ovarian carcinosarcoma (OCS) and identify its molecular characteristics. scRNA-seq was performed in resected primary OCS for an in-depth analysis of tumor cells and the tumor microenvironment. Immunohistochemistry staining was used for validation. The scRNA-seq data of OCS were compared with those of high-grade serous ovarian carcinoma (HGSOC) tumors and other OCS tumors. Both malignant epithelial and malignant mesenchymal cells were observed in the OCS patient of this study. We identified four epithelial cell subclusters with different biological roles. Among them, epithelial subcluster 4 presented high levels of breast cancer type 1 susceptibility protein homolog ( This study provides the single-cell transcriptomics signature of human OCS, which constitutes a new resource for elucidating OCS diversity.

LG-ESSs and HG-ESSs: underlying molecular alterations and potential therapeutic strategies

Endometrial stromal tumors (ESTs) include endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma (LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS), and undifferentiated uterine sarcoma (UUS). Since these are rare tumor types, there is an unmet clinical need for the systematic therapy of advanced LG-ESS or HG-ESS. Cytogenetic and molecular advances in ESTs have shown that multiple recurrent gene fusions are present in a large proportion of LG-ESSs, and HG-ESSs are identified by the tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon (

A novel defined risk signature of endoplasmic reticulum stress-related genes for predicting the prognosis and immune infiltration status of ovarian cancer

Endoplasmic reticulum (ER) stress, as an emerging hallmark feature of cancer, has a considerable impact on cell proliferation, metastasis, invasion, and chemotherapy resistance. Ovarian cancer (OvCa) is one of the leading causes of cancer-related mortality across the world due to the late stage of disease at diagnosis. Studies have explored the influence of ER stress on OvCa in recent years, while the predictive role of ER stress-related genes in OvCa prognosis remains unexplored. Here, we enrolled 552 cases of ER stress-related genes involved in OvCa from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts for the screening of prognosis-related genes. The least absolute shrinkage and selection operator (LASSO) regression was applied to establish an ER stress-related risk signature based on the TCGA cohort. A seven-gene signature revealed a favorable predictive efficacy for the TCGA, International Cancer Genome Consortium (ICGC), and another GEO cohort (

Cyclooxygenase-2 promotes ovarian cancer cell migration and cisplatin resistance via regulating epithelial mesenchymal transition

Drug-resistance and metastasis are major reasons for the high mortality of ovarian cancer (OC) patients. Cyclooxygenase-2 (COX-2) plays a critical role in OC development. This study was designed to evaluate the effects of COX-2 on migration and cisplatin (cis-dichloro diammine platinum, CDDP) resistance of OC cells and explore its related mechanisms. Cell counting kit-8 (CCK-8) assay was used to detect the cytotoxicity effects of celecoxib (CXB) and CDDP on SKOV3 and ES2 cells. The effect of COX-2 on migration was evaluated via the healing test. Western blot and real-time quantitative polymerase chain reaction (qPCR) were used to analyze E-cadherin, vimentin, Snail, and Slug levels. COX-2 promoted drug-resistance and cell migration. CXB inhibited these effects. The combination of CDDP and CXB increased tumor cell sensitivity, reduced the amount of CDDP required, and shortened treatment administration time. COX-2 upregulation increased the expression of Snail and Slug, resulting in E-cadherin expression downregulation and vimentin upregulation. COX-2 promotes cancer cell migration and CDDP resistance and may serve as a potential target for curing OC.