scholarly journals High-grade Ovarian Cancer Associated H/ACA snoRNAs Promote Cancer Cell Proliferation and Survival

2021 ◽  
Author(s):  
Laurence Faucher-Giguere ◽  
Audrey Roy ◽  
Gabrielle Deschamps-Francoeur ◽  
Sonia Couture ◽  
Ryan M Nottingham ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Cell Proliferation ◽  
High Grade ◽  
Ovarian Carcinomas ◽  
Ovarian Cancer Cell Lines ◽  
Nucleolar Rnas ◽  
Host Genes

Small nucleolar RNAs (snoRNAs) are an omnipresent class of non-coding RNAs involved in the modification and processing of ribosomal RNA (rRNA). As snoRNAs are required for ribosome production, the increase of which is a hallmark of cancer development, their expression would be expected to increase in proliferating cancer cells. However, the nature and extent of snoRNAs contribution to the biology of cancer cells remain largely unexplored. In this study, we examined the abundance patterns of snoRNA in high-grade serous ovarian carcinomas (HGSC) and serous borderline tumours (SBT) and identified a subset of snoRNA associated with increased invasiveness. This subgroup of snoRNA accurately discriminates between SBT and HGSC underlining their potential as biomarkers of tumour aggressiveness. Remarkably, knockdown of HGSC-associated H/ACA snoRNAs, but not their host genes, inhibits cell proliferation and induces apoptosis of model ovarian cancer cell lines. Wound healing and cell migration assays confirmed the requirement of these HGSC-associated snoRNA for cell invasion and increased tumour aggressiveness. Together our data indicate that H/ACA snoRNAs promote tumour aggressiveness through the induction of cell proliferation and resistance to apoptosis.

scholarly journals Follicle-Stimulating Hormone Is an Autocrine Regulator of the Ovarian Cancer Metastatic Niche Through Notch Signaling

2018 ◽  
Vol 3 (2) ◽  
pp. 340-357 ◽  
Author(s):  
Sakshi Gera ◽  
Sandeep Kumar S. ◽  
Shalini N Swamy ◽  
Rahul Bhagat ◽  
Annapurna Vadaparty ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Notch Signaling ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Fsh Receptor ◽  
Ovarian Cancer Cell Lines ◽  
Tumor Tissues

Abstract The association between the upregulated Notch and FSH signaling and ovarian cancer is well documented. However, their signaling has been investigated independently and only in the primary tumor tissues. The aim of this study was to investigate the interactive effects of FSH and Notch signaling on ovarian cancer proliferation, formation, and maintenance of disseminated ovarian cancer cells. The roles of Notch and FSH in ovarian cancer pathogenesis were investigated with ovarian cancer cell lines and specific antibodies against Notch and FSH receptor (FSHR). FSH upregulated Notch signaling and proliferation in ovarian cancer cells. High levels of FSH were detected in the ascites of patients with serous ovarian adenocarcinoma. Spheroids from the patients’ ascites, as well as the spheroids from ovarian cancer cell lines under low attachment culture conditions, expressed FSHβ subunit mRNA and secreted the hormone into the medium. In contrast, primary ovarian tumor tissues and cell line monolayers expressed very low levels of FSHβ. Ovarian cancer cell spheroids also exhibited higher expression of FSH receptor and Notch downstream genes than their monolayer counterparts. A combination of FSHR and Notch antagonistic antibodies significantly inhibited spheroid formation and cell proliferation in vitro. This study demonstrates that spheroids in ascites express and secrete FSH, which regulates cancer cell proliferation and spheroidogenesis through Notch signaling, suggesting that FSH is an autocrine regulator of cancer metastasis. Furthermore, Notch and FSHR are potential immunotherapeutic targets for ovarian cancer treatment.

scholarly journals Extracellular vesicle-derived miR-320a targets ZC3H12B to inhibit tumorigenesis, invasion, and angiogenesis in ovarian cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yan Huang ◽  
Midie Xu ◽  
Chuyu Jing ◽  
Xiaohua Wu ◽  
Xiaojun Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Extracellular Vesicle ◽  
Cancer Cell Proliferation ◽  
Promote Cell Proliferation ◽  
Ovarian Cancer Cell Lines ◽  
Lower Expression

AbstractExtracellular vesicles (EVs) play crucial roles in intercellular communication. miRNAs derived from EVs emerge as promising diagnostic indicators and therapeutic targets in a variety of malignancies. Tremendous studies have revealed the function of miRNAs derived from EVs in tumorigenesis, metastasis and other aspects. The mechanism of action of EV-derived miRNAs, however, in ovarian cancer remains largely unknown. In this study, EVs were enriched from the ovarian cancer cell lines. EVs as a whole could promote cell proliferation, invasion and new vasculature formation. However, the down-regulated EV-derived miR-320a was demonstrated to potentially suppress tumorigenesis, metastasis and angiogenesis. Moreover, EV-derived miR-320a has been proved to directly regulate a previously unknown target, ZC3H12B. An unreported role of ZC3H12B in promoting ovarian cancer cell proliferation has been elucidated and miR-320a could mediate the expression of ZC3H12B, thereby inhibiting the downstream response. As for the practical clinic values, lower expression of EV-derived miR-320a correlates with shorter survival period, indicating that EV-derived miR-320a may also serve as a prognostic biomarker in ovarian cancer. This research provides new insight into the molecular mechanism of EV-derived miR-320a in ovarian cancer and may provide new therapeutic and prognostic strategies for ovarian cancer treatment.

scholarly journals Combining ReACp53 with Carboplatin to Target High-Grade Serous Ovarian Cancers

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5908
Author(s):  
Adam Neal ◽  
Tiffany Lai ◽  
Tanya Singh ◽  
Neela Rahseparian ◽  
Tristan Grogan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Synergistic Effects ◽  
Ovarian Cancer Cells ◽  
High Grade ◽  
Ovarian Carcinomas ◽  
Ovarian Cancer Cell Lines ◽  
Poor Outcomes

Ovarian malignancies are a leading cause of cancer-related death for US women. High-grade serous ovarian carcinomas (HGSOCs), the most common ovarian cancer subtype, are aggressive tumors with poor outcomes. Mutations in TP53 are common in HGSOCs, with a subset resulting in p53 aggregation and misregulation. ReACp53 is a peptide designed to inhibit mutant p53 aggregation and has been shown efficacious in targeting cancer cells in vitro and in vivo. As p53 regulates apoptosis, combining ReACp53 with carboplatin represents a logical therapeutic strategy. The efficacy of this combinatorial approach was tested in eight ovarian cancer cell lines and 10 patient HGSOC samples using an in vitro organoid drug assay, with the SynergyFinder tool utilized for calculating drug interactions. Results demonstrate that the addition of ReACp53 to carboplatin enhanced tumor cell targeting in the majority of samples tested, with synergistic effects measured in 2 samples, additivity measured in 14 samples, and antagonism measured in 1 sample. This combination was found to be synergistic in OVCAR3 ovarian cancer cells in vitro through enhanced apoptosis, and survival of mice bearing OVCAR3 intraperitoneal xenografts was extended when treated with the addition of ReACp53 to carboplatin versus carboplatin alone. Results suggest that carboplatin and ReACp53 may be a potential strategy in targeting a subset of HGSOCs.

scholarly journals Follicle stimulating hormone is an autocrine regulator of the ovarian cancer metastatic niche through Notch signaling

2018 ◽  
Author(s):  
Sakshi Gera ◽  
Sandeep Kumar S ◽  
Shalini N. Swamy ◽  
Rahul Bhagat ◽  
Annapurna Vadaparty ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Notch Signaling ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Fsh Receptor ◽  
Ovarian Cancer Cell Lines ◽  
Tumor Tissues

AbstractThe association between the upregulated Notch and FSH signaling and ovarian cancer is well documented. However, their signaling has been investigated independently and only in the primary tumor tissues. The aim of this study was to investigate the interactive effects of FSH and Notch signaling on the ovarian cancer proliferation, formation and maintenance of the disseminated ovarian cancer cells. Roles of Notch and FSH in the ovarian cancer pathogenesis was investigated using ovarian cancer cell lines and specific antibodies against Notch and FSH receptor (FSHR). FSH upregulated Notch signaling and proliferation in the ovarian cancer cells. High levels of FSH were detected in the ascites of patients with serous ovarian adenocarcinoma. The spheroids from the ascites of the patients, as well as, the spheroids from the ovarian cancer cell lines under low attachment culture conditions, expressed FSHβ subunit mRNAs and secreted the hormone into the medium. In contrast, the primary ovarian tumor tissues and cell line monolayers expressed very low levels of FSHβ. The ovarian cancer cell spheroids also exhibited higher expression of the FSH receptor and Notch downstream genes than their monolayer counterparts. A combination of FSHR and Notch antagonistic antibodies significantly inhibited spheroid formation and cell proliferation in vitro. This study demonstrates that spheroids in ascites express and secrete FSH, which regulates cancer cell proliferation and spheroidogenesis through Notch signaling, suggesting that FSH is an autocrine regulator of cancer metastasis. Further, Notch and FSHR are potential immunotherapeutic targets for ovarian cancer treatment.

scholarly journals Oleanolic Acid (OA) Targeting UNC5B Inhibits Proliferation and EMT of Ovarian Cancer Cell and Increases Chemotherapy Sensitivity of Niraparib

2022 ◽  
Vol 2022 ◽  
pp. 1-12
Author(s):  
Zhen Zeng ◽  
Jing Yu ◽  
Zhongqing Jiang ◽  
Ningwei Zhao
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Cancer Cell Proliferation ◽  
Mesenchymal Transition ◽  
Ovarian Epithelial Cells

Objective. To investigate the effect of OA on proliferation, migration, and epithelial-mesenchymal transition (EMT) of ovarian cancer cells by inhibiting UNC5B and to study its mechanism. Methods. TCGA database was used to analyze the expression of UNC5B in ovarian cancer and its relationship with prognosis. The expression of UNC5B in ovarian cancer cells was detected by qPCR assay. qRT-PCR was used to detect the changes of EMT markers after different treatments. CCK-8 assay was used to detect cell proliferation, transwell assay was used to evaluate cell migration, and clonogenesis assay was used to evaluate the effect of UNC5B on ovarian cancer cell proliferation. Meanwhile, the synergistic effect of OA on niraparib was evaluated. Results. UNC5B was highly expressed in ovarian cancer, and its expression was negatively correlated with the prognosis of ovarian cancer patients. UNC5B was highly expressed in ovarian cancer cells SKOV3 and OVCA420 compared with normal ovarian epithelial cells. In addition, silencing UNC5B inhibits the proliferation, invasion, clonogenesis, and EMT processes of ovarian cancer cells. OA inhibits proliferation, invasion, and clonogenesis of ovarian cancer cells by inhibiting UNC5B and increases the antitumor activity of niraparib. Conclusion. UNC5B acts as an oncogenic gene in ovarian cancer. OA inhibits ovarian cancer cell proliferation, migration, and EMT by targeting UNC5B and increases the antitumor effect of niraparib. UNC5B is expected to be a new potential therapeutic target for ovarian cancer. OA may be used as an antitumor drug and deserves further study.

scholarly journals Extracellular Vesicle-derived miR-320a Targets ZC3H12B to Inhibit Tumorigenesis, Invasion, and Angiogenesis in Ovarian Cancer

2021 ◽  
Author(s):  
Yan Huang ◽  
Midie Xu ◽  
Chuyu Jing ◽  
Xiaohua Wu ◽  
Xiaojun Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Extracellular Vesicle ◽  
Cancer Cell Proliferation ◽  
Promote Cell Proliferation ◽  
Ovarian Cancer Cell Lines ◽  
Lower Expression

Abstract Extracellular vesicles (EVs) play crucial roles in intercellular communication. miRNAs derived from EVs emerge as promising diagnostic indicators and therapeutic targets in a variety of malignancies. Tremendous studies have revealed the function of miRNAs derived from EVs in tumorigenesis, metastasis and other aspects. The mechanism of action of EV-derived miRNAs, however, in ovarian cancer remains largely unknown. In this study, EVs were enriched from the ovarian cancer cell lines. EVs as a whole could promote cell proliferation, invasion and new vasculature formation. However, the down-regulated EV-derived miR-320a was demonstrated to potentially suppress tumorigenesis, metastasis and angiogenesis. . Moreover, EV-derived miR-320a has been proved to directly regulate a previously unknown target, ZC3H12B. An unreported role of ZC3H12B in promoting ovarian cancer cell proliferation has been elucidated and miR-320a could mediate the expression of ZC3H12B, thereby inhibiting the downstream response. As for the practical clinic values, lower expression of EV-derived miR-320a correlates with shorter survival period, indicating that EV-derived miR-320a may also serve as a prognostic biomarker in ovarian cancer. This research provides new insight into the molecular mechanism of EV-derived miR-320a in ovarian cancer and may provide new therapeutic and prognostic strategies for ovarian cancer treatment.

scholarly journals How can food extracts consumed in the Mediterranean and East Asia suppress prostate cancer proliferation?

2011 ◽  
Vol 108 (3) ◽  
pp. 424-430 ◽  
Author(s):  
Mu Yao ◽  
Chanlu Xie ◽  
Maryrose Constantine ◽  
Sheng Hua ◽  
Brett D. Hambly ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
East Asia ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Prostate Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Prostate Cancer Cells ◽  
The Mediterranean

We have developed a blend of food extracts commonly consumed in the Mediterranean and East Asia, named blueberry punch (BBP), with the ultimate aim to formulate a chemoprevention strategy to inhibit prostate cancer progression in men on active surveillance protocol. We demonstrated previously that BBP inhibited prostate cancer cell proliferation in vitro and in vivo. The purpose of this study was to determine the molecular mechanism responsible for the suppression of prostate cancer cell proliferation by BBP. Treatment of lymph node-metastasised prostate cancer cells (LNCaP) and bone-metastasised prostate cancer cells (PC-3 and MDA-PCa-2b) with BBP (up to 0·8 %) for 72 h increased the percentage of cells at the G0/G1 phase and decreased those at the S and G2/M phases. The finding was supported by the reduction in the percentage of Ki-67-positive cells and of DNA synthesis measured by the incorporation of 5-ethynyl-2′-deoxyuridine. Concomitantly, BBP treatment decreased the protein levels of phosphorylated retinoblastoma, cyclin D1 and E, cyclin-dependent kinase (CDK) 4 and 2, and pre-replication complex (CDC6 and MCM7) in LNCaP and PC-3 cells, whereas CDK inhibitor p27 was elevated in these cell lines. In conclusion, BBP exerts its anti-proliferative effect on prostate cancer cells by modulating the expression and phosphorylation of multiple regulatory proteins essential for cell proliferation.

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