scholarly journals Single-cell analysis revealed that IL4I1 promoted ovarian cancer progression

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hongyu Zhao ◽  
Yu Teng ◽  
Wende Hao ◽  
Jie Li ◽  
Zhefeng Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Single Cell ◽  
Cancer Progression ◽  
Cox Regression ◽  
Single Cell Analysis ◽  
Cell Types ◽  
In Vitro Assays ◽  
Migration And Invasion ◽  
Dominant Type

Abstract Background Ovarian cancer was one of the leading causes of female deaths. Patients with OC were essentially incurable and portends a poor prognosis, presumably because of profound genetic heterogeneity limiting reproducible prognostic classifications. Methods We comprehensively analyzed an ovarian cancer single-cell RNA sequencing dataset, GSE118828, and identified nine major cell types. Relationship between the clusters was explored with CellPhoneDB. A malignant epithelial cluster was confirmed using pseudotime analysis, CNV and GSVA. Furthermore, we constructed the prediction model (i.e., RiskScore) consisted of 10 prognosis-specific genes from 2397 malignant epithelial genes using the LASSO Cox regression algorithm based on public datasets. Then, the prognostic value of Riskscore was assessed with Kaplan–Meier survival analysis and time-dependent ROC curves. At last, a series of in-vitro assays were conducted to explore the roles of IL4I1, an important gene in Riskscore, in OC progression. Results We found that macrophages possessed the most interaction pairs with other clusters, and M2-like TAMs were the dominant type of macrophages. C0 was identified as the malignant epithelial cluster. Patients with a lower RiskScore had a greater OS (log-rank P < 0.01). In training set, the AUC of RiskScore was 0.666, 0.743 and 0.809 in 1-year, 3-year and 5-year survival, respectively. This was also validated in another two cohorts. Moreover, downregulation of IL4I1 inhibited OC cells proliferation, migration and invasion. Conclusions Our work provide novel insights into our understanding of the heterogeneity among OCs, and would help elucidate the biology of OC and provide clinical guidance in prognosis for OC patients.

scholarly journals The polypeptide GALNT6 Displays Redundant Functions upon Suppression of its Closest Homolog GALNT3 in Mediating Aberrant O-Glycosylation, Associated with Ovarian Cancer Progression

2019 ◽  
Vol 20 (9) ◽  
pp. 2264 ◽  
Author(s):  
Razan Sheta ◽  
Magdalena Bachvarova ◽  
Elizabeth Macdonald ◽  
Stephane Gobeil ◽  
Barbara Vanderhyden ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Survival Rates ◽  
Functional Redundancy ◽  
Tumor Formation ◽  
Migration And Invasion ◽  
Gene Ablation

Epithelial ovarian cancer (EOC) represents the most lethal gynecologic malignancy; a better understanding of the molecular mechanisms associated with EOC etiology could substantially improve EOC management. Aberrant O-glycosylation in cancer is attributed to alteration of N-acetylgalactosaminyltransferases (GalNAc-Ts). Reports suggest a genetic and functional redundancy between GalNAc-Ts, and our previous data are indicative of an induction of GALNT6 expression upon GALNT3 suppression in EOC cells. We performed single GALNT3 and double GALNT3/T6 suppression in EOC cells, using a combination of the CRISPR-Cas9 system and shRNA-mediated gene silencing. The effect of single GALNT3 and double GALNT3/T6 inhibition was monitored both in vitro (on EOC cells roliferation, migration, and invasion) and in vivo (on tumor formation and survival of experimental animals). We confirmed that GALNT3 gene ablation leads to strong and rather compensatory GALNT6 upregulation in EOC cells. Moreover, double GALNT3/T6 suppression was significantly associated with stronger inhibitory effects on EOC cell proliferation, migration, and invasion, and accordingly displayed a significant increase in animal survival rates compared with GALNT3-ablated and control (Ctrl) EOC cells. Our data suggest a possible functional redundancy of GalNAc-Ts (GALNT3 and T6) in EOC, with the perspective of using both these enzymes as novel EOC biomarkers and/or therapeutic targets.

scholarly journals EPDR1, Which Is Negatively Regulated by miR-429, Suppresses Epithelial Ovarian Cancer Progression via PI3K/AKT Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhendan Zhao ◽  
Zhiling Wang ◽  
Pengling Wang ◽  
Shujie Liu ◽  
Yingwei Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Figo Stage ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Gynecology And Obstetrics

Epithelial ovarian cancer (EOC) is the main pathological type of ovarian cancer. In this study, we found that ependymin-related 1 (EPDR1) was remarkably downregulated in EOC tissues, and low EPDR1 expression was associated with International Federation of Gynecology and Obstetrics (FIGO) stage, metastasis, and poor prognosis. We confirmed that EPDR1 overexpression dramatically suppressed EOC cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, EPDR1 inhibited EOC tumorigenesis and progression, at least in part, through the repression of the PI3K (Phosphoinositide 3-kinase)/AKT (AKT Serine/Threonine Kinase 1) signaling pathway. Furthermore, the expression and function of EPDR1 were regulated by miR-429, as demonstrated by luciferase reporter assays and rescue experiments. In conclusion, our study validated that EPDR1, negatively regulated by miR-429, played an important role as a tumor-suppressor gene in EOC development via inhibition of the PI3K/AKT pathway. The miR-429/EPDR1 axis might provide novel therapeutic targets for individualized treatment of EOC patients in the future.

scholarly journals Lineage specification and plasticity in CD19− early B cell precursors

2006 ◽  
Vol 203 (3) ◽  
pp. 675-687 ◽  
Author(s):  
Lynn L. Rumfelt ◽  
Yan Zhou ◽  
Benjamin M. Rowley ◽  
Susan A. Shinton ◽  
Richard R. Hardy
Keyword(s):  
B Cell ◽  
Single Cell ◽  
Single Cell Analysis ◽  
Expression Profiles ◽  
In Vitro Assays ◽  
Mouse Bone Marrow ◽  
Lineage Specification ◽  
Color Flow ◽  
B Lineage

We describe here three CD19− B cell precursor populations in mouse bone marrow identified using 12-color flow cytometry. Cell transfer experiments indicate lineage potentials consistent with multilineage progenitor (MLP), common lymphoid progenitor (CLP), and B lineage–restricted pre-pro–B (Fr. A), respectively. However, single cell in vitro assays reveal lineage plasticity: lymphoid/myeloid lineage potential for CLP and B/T lineage potential for Fr. A. Despite myeloid potential, recombination activating gene 2 reporter activation is first detected at low levels in most MLP cells, with 95% of CLPs showing 10-fold increased levels. Furthermore, single cell analysis shows that half of CLP and 90% of Fr. A cells contain heavy chain DJ rearrangements. These data, together with expression profiles of lineage-specific genes, demonstrate progressive acquisition of B lineage potential and support an asynchronous view of early B cell development, in which B lineage specification initiates in the MLP/CLP stage, whereas myeloid potential is not lost until the pre-pro–B (Fr. A) stage, and B/T lymphoid plasticity persists until the CD19+ pro–B stage. Thus, MLP, CLP, and Fr. A represent progressively B lineage–specified stages in development, before the CD19+ B lineage–committed pro–B stage.

scholarly journals Inhibitory Effect of Etravirine, a Non-Nucleoside Reverse Transcriptase Inhibitor, via Anterior Gradient Protein 2 Homolog Degradation against Ovarian Cancer Metastasis

2022 ◽  
Vol 23 (2) ◽  
pp. 944
Author(s):  
Thanh Truong Giang Ly ◽  
Jisoo Yun ◽  
Jong-Seong Ha ◽  
Yeon-Ju Kim ◽  
Woong-Bi Jang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Reverse Transcriptase ◽  
Cancer Progression ◽  
Nucleoside Reverse Transcriptase Inhibitor ◽  
Cancer Metastasis ◽  
Transcriptase Inhibitor ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Reverse Transcriptase Inhibitor

Anterior gradient protein 2 homolog (AGR2), an endoplasmic reticulum protein, is secreted in the tumor microenvironment. AGR2 is a member of the disulfide isomerase family, is highly expressed in multiple cancers, and promotes cancer metastasis. In this study, we found that etravirine, which is a non-nucleoside reverse transcriptase inhibitor, could induce AGR2 degradation via autophagy. Moreover, etravirine diminished proliferation, migration, and invasion in vitro. Moreover, in an orthotopic xenograft mouse model, the combination of etravirine and paclitaxel significantly suppressed cancer progression and metastasis. This drug may be a promising therapeutic agent for the treatment of ovarian cancer.

scholarly journals CYPA promotes the progression and metastasis of serous ovarian cancer (SOC) in vitro and in vivo

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhi-Ying Qi ◽  
Fang Wang ◽  
Ying-Ying Yue ◽  
Xue-Wang Guo ◽  
Rui-Meng Guo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Immune Modulation ◽  
Clinical Stage ◽  
Migration And Invasion ◽  
Serous Ovarian Cancer ◽  
Promising Therapeutic Target ◽  
Lymphnode Metastasis

AbstractOvarian cancer (OC) is a type of gynaecological malignancy with high mortality in females. Serous ovarian cancer (SOC) is a distinct subtype of OC with poor early diagnosis. Given the limitations of traditional therapies, such as chemotherapy, targeted treatment is therefore a promising therapy to improve the survival rate of SOC patients. Cyclophilin A (CYPA) is a member of Cyclophilin family and thought to participates in multiple cellular processes such as cell transduction and immune modulation. Recently, various of studies indicated that CYPA has critical impact on cancer progression. CYPA could regulate cell proliferation, invasion, and chemoresistance of multiple types of cancers. However, it is still unclear whether it could affect ovarian cancer. In this study, we demonstrated that CYPA was highly expressed in SOC tissues compared with adjacent tissues. Further, CYPA was significantly associated with clinical stage and lymphnode metastasis of SOC patients. Additionally, data indicated that knockdown of CYPA by its shRNA dramatically reduces migration and invasion capacity of SOC cells in vitro and blocks tumor metastasis in vivo. Our study investigates the involvement of CYPA in the progression and metastasis of SOC, and therefore provides CYPA as a promising therapeutic target for SOC treatment.

scholarly journals Assessing the Heterogeneity of Cardiac Non-myocytes and the Effect of Cell Culture with Integrative Single Cell Analysis

2020 ◽  
Author(s):  
Brian S. Iskra ◽  
Logan Davis ◽  
Henry E. Miller ◽  
Yu-Chiao Chiu ◽  
Alexander R. Bishop ◽  
...  
Keyword(s):  
Cell Culture ◽  
Single Cell ◽  
Single Cell Analysis ◽  
Cell Types ◽  
Cell Analysis ◽  
Mass Cytometry ◽  
Single Cell Rna Sequencing ◽  
High Depth

AbstractCardiac non-myocytes comprise a diverse and crucial cell population in the heart that plays dynamic roles in cardiac wound healing and growth. Non-myocytes broadly fall into four cell types: endothelium, fibroblasts, leukocytes, and pericytes. Here we characterize the diversity of the non-myocytes in vivo and in vitro using mass cytometry. By leveraging single-cell RNA sequencing we inform the design of a mass cytometry panel. To aid in annotation of the mass cytometry datasets, we utilize data integration with a neural network. We introduce approximately 460,000∼ single cell proteomes of non-myocytes as well as 5,000∼ CD31 negative single cell transcriptomes. Using our data, as well as previously reported datasets, we characterize cardiac non-myocytes with high depth in six mice, characterizing novel surface markers (CD9, CD200, Notch3, and FolR2). Further, we find that extended cell culture promotes the proliferation of CD45+CD11b+FolR2+IAIE- myeloid cells in addition to fibroblasts.

scholarly journals CAF-derived HGF promotes cell proliferation and drug resistance by up-regulating the c-Met/PI3K/Akt and GRP78 signalling in ovarian cancer cells

2017 ◽  
Vol 37 (2) ◽  
Author(s):  
Wei Deying ◽  
Geng Feng ◽  
Liang Shumei ◽  
Zhao Hui ◽  
Liu Ming ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cell Types ◽  
Tumour Microenvironment ◽  
Ovarian Cancer Cells ◽  
Phosphoinositide 3 Kinase

The tumour microenvironment is a highly heterogeneous entity that plays crucial roles in cancer progression. As the most prominent stromal cell types, cancer-associated fibroblasts (CAFs) produce a variety of factors into the tumour microenvironment. In the present study, we firstly isolated CAFs from tumour tissues of the patients with ovarian cancer and demonstrated that the hepatocyte growth factor (HGF) was highly expressed in the supernatants of CAFs. CAF-derived HGF or human recombinant HGF promoted cell proliferation in human ovarian cell lines SKOV3 and HO-8910 cells. Western blotting analysis also showed that CAF-derived HGF or recombinant HGF activated c-Met/phosphoinositide 3-kinase (PI3K)/Akt and glucose-regulated protein 78 (GRP78) signalling pathways in ovarian cancer cells, and these effects could be abrogated by anti-HGF and c-Met inhibitor INCB28060. Moreover, HGF in CAF matrix attenuated paclitaxel (PAC)-caused inhibition of cell proliferation and increase in cell apoptosis through activating c-Met/PI3K/Akt and GRP78 pathways in SKOV3 and HO-8910 cells. The results in vitro were further validated in nude mice. These findings suggest that CAF-derived HGF plays crucial roles in cell proliferation and drug resistance in ovarian cancer cells.

scholarly journals MicroRNA-320a Promotes Epithelial Ovarian Cancer Cell Proliferation and Invasion by Targeting RASSF8

2021 ◽  
Vol 11 ◽  
Author(s):  
Lili Zhang ◽  
Huixiao Chen ◽  
Fengxi He ◽  
Shiqian Zhang ◽  
Aihua Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Target Gene ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation

MicroRNAs (miRNAs) play important roles in tumorigenesis by controlling target gene expression. With opposing roles as a tumor suppressor or oncogene, microRNA-320a (miR-320a) was found to participate in tumor genesis and progression and also identified as a potentially useful marker in cancer diagnosis, treatment, and prognosis. To better understand the role of miR-320a in ovarian cancer, we investigated miR-320a expression in epithelial ovarian cancer (EOC) specimens as well as EOC cell lines and analyzed correlations between miR-320a expression and processes associated with EOC progression. The miR-320a level in EOC specimens was found to be associated with ovarian cancer progression and infiltration. Through in vitro and in vivo studies, we found that miR-320a significantly promoted the proliferation, migration, and invasion of EOC cells, and we identified RASSF8 as a target gene of miR-320a that was downregulated in EOC tissues and cell lines. In vitro downregulation of RASSF8 promoted the growth, migration, and invasion of EOC cells. Together these findings indicate that RASSF8 is a direct target of miR-320a, through which miR-320a promotes the progression of EOC.

scholarly journals MicroRNA-125b Suppresses Ovarian Cancer Progression via Suppression of the Epithelial-Mesenchymal Transition Pathway by Targeting the SET Protein

2016 ◽  
Vol 39 (2) ◽  
pp. 501-510 ◽  
Author(s):  
Xiaoyan Ying ◽  
Kuang Wei ◽  
Zhe Lin ◽  
Yugui Cui ◽  
Jie Ding ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Chemotherapy Resistance ◽  
Ectopic Expression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Background/Aims: MicroRNA-125b (miR-125b) is overexpressed in several types of cancer and contributes to chemotherapy resistance. However, its role in epithelial ovarian carcinoma remains unknown. The goal of this study was to identify the relationship between miR-125b and the epithelial-mesenchymal transition (EMT) in ovarian cancer. Methods: In total, 55patients with epithelial ovarian cancer (EOC) were included in our study. The relative expression of miR-125b was measured using real-time polymerase chain reaction (RT-PCR).The protein expression of SET and EMT-related indicators in cell lines were assessed by Western blot. The regulation of SET by miR-125b was confirmed using luciferase reporter assays. The effect of miR-125b on metastasis was evaluated using an in vivo metastasis model. Results: miR-125b expression was markedly lower in the EOC specimens. Ectopic expression of miR-125b in EOC cells significantly inhibited tumor invasion.miR-125b expression was negatively associated with both EMT and SET expression, in vivo and in vitro. Mechanistic studies identified SET as a direct target of miR-125b, and the downregulation of SET, observed during tumor migration, was affected by the overexpression of miR125b. Conclusion: miR-125b suppresses EOC cell migration and invasion by targeting the SET protein, and this study may provide a novel mechanism for understanding the progression of EOC.

Sign in / Sign up

Export Citation Format

Share Document