Correction to: High expression of HO-1 predicts poor prognosis of ovarian cancer patients and promotes proliferation and aggressiveness of ovarian cancer cells

Abstract Background Emerging evidence has shown that circular RNAs (circRNAs) play essential roles in cancer biology and are potential biomarkers and targets for cancer therapy. However, the expression and function of circRNAs in ovarian carcinogenesis and its progression remain elusive. Methods RNA sequencing was performed to reveal circRNA expression profiles in ovarian cancerous and normal tissues. Single-molecule RNA in-situ hybridization was used to quantify circPLEKHM3 expression in tumor tissues. Cell-based in-vitro and in-vivo assays were subsequently conducted to support the clinical findings. Results CircPLEKHM3 was identified as one of the most significantly down-regulated circRNAs in ovarian cancer tissues compared with normal tissues. Its expression was further decreased in peritoneal metastatic ovarian carcinomas compared to primary ovarian carcinomas. Patients with lower circPLEKHM3 tend to have a worse prognosis. Functionally, circPLEKHM3 overexpression inhibited cell growth, migration and epithelial–mesenchymal transition, whereas its knockdown exerted an opposite role. Further analyses showed that circPLEKHM3 sponged miR-9 to regulate the endogenous expression of BRCA1, DNAJB6 and KLF4, and consequently inactivate AKT1 signaling. In addition, AKT inhibitor MK-2206 could block the tumor-promoting effect of circPLEKHM3 depletion, and potentiate Taxol-induced growth inhibition of ovarian cancer cells. Conclusions Our findings demonstrated that circPLEKHM3 functions as a tumor suppressor in ovarian cancer cells by targeting the miR-9/BRCA1/DNAJB6/KLF4/AKT1 axis and may be used as a prognostic indicator and therapeutic target in ovarian cancer patients. The new strategy for treating ovarian cancer by a combination therapy of Taxol with MK-2206 is worth further investigation, especially in ovarian cancer patients with loss of circPLEKHM3 expression.

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Cyclooxygenase 2 Promotes Proliferation and Invasion in Ovarian Cancer Cells via the PGE2/NF-κB Pathway

Cell Transplantation ◽

10.1177/0963689719890597 ◽

2019 ◽

Vol 28 (1_suppl) ◽

pp. 1S-13S ◽

Cited By ~ 4

Author(s):

Xiao Zhang ◽

Keqin Yan ◽

Lin Deng ◽

Jing Liang ◽

Haiyan Liang ◽

...

Keyword(s):

Ovarian Cancer ◽

Prostaglandin E2 ◽

Cancer Cells ◽

Nuclear Factor Kappa B ◽

Cyclooxygenase 2 ◽

High Expression ◽

Ovarian Cancer Cells ◽

Nuclear Factor ◽

Nuclear Factor Kappa ◽

Proliferation And Invasion

Ovarian cancer is the leading cause of death among gynecological malignancies. Cyclooxygenase 2 is widely expressed in various cancer cells and participates in the occurrence and development of tumors by regulating a variety of downstream signaling pathways. However, the function and molecular mechanisms of cyclooxygenase 2 remain unclear in ovarian cancer. Here, we demonstrated that cyclooxygenase 2 was highly expressed in ovarian cancer and the expression level was highly correlated with ovarian tumor grades. Further, ovarian cancer cells with high expression of cyclooxygenase 2 exhibit enhanced proliferation and invasion abilities. Specifically, cyclooxygenase 2 promoted the release of prostaglandin E2 upregulated the phosphorylation levels of phospho-nuclear factor-kappa B p65. Celecoxib, AH6809, and BAY11-7082 all can inhibit the promoting effect of cyclooxygenase 2 on SKOV3 and OVCAR3 cell proliferation and invasion. Besides, celecoxib inhibited SKOV3 cell growth in the xenograft tumor model. These data suggest that high expression of cyclooxygenase 2 promotes the proliferation and invasion of ovarian cancer cells through the prostaglandin E2/nuclear factor-kappa B signaling pathway. Cyclooxygenase 2 may be a potential therapeutic target for the treatment of ovarian cancer.

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Overexpression of BMPER in Ovarian Cancer and the Mechanism by which It Promotes Malignant Biological Behavior in Tumor Cells

BioMed Research International ◽

10.1155/2020/3607436 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Yong Xi ◽

Xin Nie ◽

Jing Wang ◽

Lingling Gao ◽

Bei Lin

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Tumor Cells ◽

Poor Prognosis ◽

Malignant Tumors ◽

Biological Behavior ◽

Ovarian Cancer Cells ◽

Epithelial Tumor ◽

Tumor Tissues ◽

Ovarian Epithelial Tumor

Background. BMPER has been reported to be associated with the biological behavior of a few malignant tumors, but the mechanism is still unclear. We aimed to detect BMPER expression in ovarian epithelial tumor tissues and its effects on their biological behaviors, as well as to elucidate the possible mechanism. Methods. BMPER expression in ovarian epithelial tumor tissues was detected by immunohistochemistry. BMPER expression in ovarian cancer cell lines was inhibited via RNA interference. Changes in the malignant behaviors of ovarian cancer cells were detected by MTT, wound healing, Transwell, and flow cytometry assays. Changes in proteins in the MAPK and autophagy-related signaling pathways were detected by Western blot analysis. Results. The expression of BMPER was significantly upregulated in ovarian epithelial malignant tumors and was related to increased lymph node metastasis and lower survival rate. High BMPER expression is an independent risk factor for poor prognosis in patients. Inhibition of BMPER inhibited the proliferation, invasion, and migration of ovarian cancer cells and promoted apoptosis. In addition, BMPER downregulation decreased the expression of PCNA, Bcl-2, MMP2, and MMP9 and increased the expression of Bax. Moreover, the levels of p-ERK, p-MEK, and the autophagy-related protein p-mTOR were decreased, and Beclin 1 levels and the LC3II/I ratio were increased. Conclusions. Our findings indicated that BMPER is closely related to poor prognosis in ovarian cancer. BMPER plays a role in promoting the malignant biological behavior of tumor cells through the MAPK and autophagy-related signaling pathways.

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GPR30 signaling to regulate epithelial-mesenchymal transition and predict survival in ovarian cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e17041 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e17041-e17041

Author(s):

Satoe Fujiwara ◽

Shinichi Terada ◽

Yuhei Kogata ◽

Hiroshi Maruoka ◽

Yoshimichi Tanaka ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Western Blotting ◽

Poor Prognosis ◽

Cancer Metastasis ◽

Kinase Inhibitor ◽

3D Culture ◽

Ovarian Cancer Cells ◽

Mesenchymal Transition ◽

Emt Markers

e17041 Background: G protein-coupled receptor 30 (GPR30) is a 7-transmembrane　estrogen receptor that functions alongside traditional estrogen receptors to regulate the cellular responses to estrogen. Recent studies suggest that the high expression of GPR30 is associated with a poor prognosis in breast cancer or endometrial cancer. Although the role of GPR30 in ovarian cancer was unclear, we revealed that GPR30 is associated with poor prognosis in ovarian cancer. On the other hand, Epithelial-to-Mesenchymal Transition (EMT) is involved in cancer metastasis. The purpose of this study is to reveal how GPR30 was associated with poor prognosis and whether associated with EMT in ovarian cancer. Methods: We examined whether GPR30 signaling activates the EGFR-Akt pathway in an ovarian cancer cell line (Caov-3) by a Western blotting analysis. We also examined the effect of GPR30 on EMT were evaluated in Caov-3, which were cultured both in two-dimensional (2D) culture and three-dimensional (3D) culture model. GPR30 agonist, G1, was used to confirm the regulatory effects of GPR30 on the change of phenotypic modulation and EMT markers expression. Results: The phosphorylation of the EGFR and Akt could be significantly enhanced by G1 (p < 0.05) and inhibited by a Src family kinase inhibitor. In 3D culture, the stimulation of GPR30 leads the floating and sphere formation in Caov-3. G1-induced EMT was observed with related regulation of EMT markers expression at both mRNA and protein level. G1 induced the decrease of E-cadherin level and the increase of Snail and Vimentin in RT-PCR and Western blotting. Knockdown of GPR30, using siRNA, blocked G1-induced EMT. Conclusions: GPR30 increases the phosphorylation of Akt via the EGFR in ovarian cancer cells and changes ovarian cancer cells to the EMT state.GPR30 might be an important molecule related to metastasis process in ovarian cancer.

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Sensitivity of EGFR/HER-2 Positive Cells Isolated from Ascitic Fluid of Advanced Ovarian Cancer Patients to EGFR/HER-2 Inhibitors

Applied Sciences ◽

10.3390/app10072343 ◽

2020 ◽

Vol 10 (7) ◽

pp. 2343

Author(s):

Kenny Chitcholtan ◽

Dianne Harker ◽

Bryony Simcock ◽

Peter Sykes

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cancer Patients ◽

Ascitic Fluid ◽

Cancer Cell ◽

Protein Level ◽

Advanced Ovarian Cancer ◽

Immunofluorescent Staining ◽

Ovarian Cancer Cells ◽

Her 2

Background: advanced ovarian cancer often presents with ascites. These ascites contain small clusters of cancer cells, which may contribute greatly to the metastatic potential of ovarian cancer in the peritoneal cavity. Therefore, understanding the unique protein expressions of this cell population will provide vital information for the development of tailored, targeted treatment. In this study, we isolate floating ovarian cancer cells from ovarian cancer patient ascitic fluid and use these cells to document that the expression of EGFR/HER-2 proteins may be essential for the growth and survival of these floating cancer cell clusters. Methods: ascitic fluid-derived cells were isolated from ascitic fluid by using Ficoll separation. Cells were cultured in a non-adherent condition for six days. The protein level of EGFR, HER-2, AKT, and ERK and their phosphorylation in ovarian cancer cell lines were determined by immunofluorescence. The immunofluorescent staining for proteins presented in ascitic fluid-derived cells determined the intensity profile of each protein using Carl Zeiss Blue software. Results: Isolated ovarian cancer cells from ascitic fluid have a measurable level of EGFR and HER-2 proteins. The inhibition of EGFR and EGFR/HER-2 positive cells with gefitinib and canertinib selectively disrupts cell viability and the protein level of EGFR, HER-2, AKT and ERK and their respective phosphorylation status. In addition, the dual EGFR/HER-2 inhibitor canertinib demonstrates greater anti-tumour effects than gefitinib in EGFR/HER-2 positive cells. Conclusion: These studies reveal an important role of multiple activation of receptor tyrosine kinases in floating ovarian cancer cells, as well as the importance of a dual EGFR/HER-2 inhibitor used as alternative adjuvant therapy in advanced ovarian cancer patients.

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Secretome Identifies Tenascin-X as a Potent Marker of Ovarian Cancer

BioMed Research International ◽

10.1155/2015/208017 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Marianne Kramer ◽

Sandra Pierredon ◽

Pascale Ribaux ◽

Jean-Christophe Tille ◽

Patrick Petignat ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cancer Patients ◽

Ca 125 ◽

Ovarian Cancer Cells ◽

Serous Ovarian Cancer ◽

Protein Biomarkers ◽

Serum Samples ◽

Cancer Tissues

CA-125 has been a valuable marker for the follow-up of ovarian cancer patients but it is not sensitive enough to be used as diagnostic marker. We had already used secretomic methods to identify proteins differentially secreted by serous ovarian cancer cells compared to healthy ovarian cells. Here, we evaluated the secretion of these proteins by ovarian cancer cells during the follow-up of one patient. Proteins that correlated with CA-125 levels were screened using serum samples from ovarian cancer patients as well as benign and healthy controls. Tenascin-X secretion was shown to correlate with CA-125 value in the initial case study. The immunohistochemical detection of increased amount of tenascin-X in ovarian cancer tissues compared to healthy tissues confirms the potent interest in tenascin-X as marker. We then quantified the tenascin-X level in serum of patients and identified tenascin-X as potent marker for ovarian cancer, showing that secretomic analysis is suitable for the identification of protein biomarkers when combined with protein immunoassay. Using this method, we determined tenascin-X as a new potent marker for serous ovarian cancer.

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Targeting CA-125 Transcription by Development of a Conditionally Replicative Adenovirus for Ovarian Cancer Treatment

Cancers ◽

10.3390/cancers13174265 ◽

2021 ◽

Vol 13 (17) ◽

pp. 4265

Author(s):

Er Yue ◽

Guangchao Yang ◽

Yuanfei Yao ◽

Guangyu Wang ◽

Atish Mohanty ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Treatment ◽

Cancer Cells ◽

Cancer Patients ◽

Essential Gene ◽

In Vivo Studies ◽

Ca 125 ◽

Ovarian Cancer Cells ◽

Specific Expression ◽

Dna Fragment

CA-125, encoded by the MUC16 gene, is highly expressed in most ovarian cancer cells and thus serves as a tumor marker for monitoring disease progression or treatment response in ovarian cancer patients. However, targeting MUC16/CA-125 for ovarian cancer treatment has not been successful to date. In the current study, we performed multiple steps of high-fidelity PCR and obtained a 5 kb DNA fragment upstream of the human MUC16 gene. Reporter assays indicate that this DNA fragment possesses transactivation activity in CA-125-high cancer cells, but not in CA-125-low cancer cells, indicating that the DNA fragment contains the transactivation region that controls specific expression of the MUC16 gene in ovarian cancer cells. We further refined the promoter and found a 1040 bp fragment with similar transcriptional activity and specificity. We used this refined MUC16 promoter to replace the E1A promoter in the adenovirus type 5 genome DNA, where E1A is an essential gene for adenovirus replication. We then generated a conditionally replicative oncolytic adenovirus (CRAd) that replicates in and lyses CA-125-high cancer cells, but not CA-125-low or -negative cancer cells. In vivo studies showed that intraperitoneal virus injection prolonged the survival of NSG mice inoculated intraperitoneally (ip) with selected ovarian cancer cell lines. Furthermore, the CRAd replicates in and lyses primary ovarian cancer cells, but not normal cells, collected from ovarian cancer patients. Collectively, these data indicate that targeting MUC16 transactivation utilizing CRAd is a feasible approach for ovarian cancer treatment that warrants further investigation.

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