scholarly journals Cocultured porcine granulosa cells respond to excess non-esterified fatty acids during in vitro maturation

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Meihong Shi ◽  
Marc-André Sirard
Keyword(s):  
Fatty Acids ◽  
Granulosa Cells ◽  
Epithelial Mesenchymal Transition ◽  
Differentially Expressed ◽  
Algorithm Analysis ◽  
Inflammatory Factors ◽  
Luteal Cell ◽  
Mesenchymal Transition ◽  
Esterified Fatty Acids

Abstract Background Non-esterified fatty acids (NEFAs) are one of the main lipid components of follicular fluid at concentrations that depend on circulating levels. Elevated levels of NEFAs impair oocyte quality, development potential, and may subsequently influence the metabolism and reproductive fitness of offspring. Granulosa cells (GCs) are the follicular cells that are closely communicating with the oocyte. However, the responses of GCs exposed to high levels of NEFAs when cocultured with cumulus-oocyte complexes (COCs), and how they attenuate the negative effects of NEFAs on oocytes, are unclear. Results To better understand this protective effect, monolayers of porcine GCs were cocultured with COCs during in vitro maturation (IVM) in the presence of elevated levels of NEFAs. Genomic expression analysis was conducted to explore the responses of the GCs to the elevated levels of NEFAs. After limma algorithm analysis, 1,013 genes were differentially expressed between GCs cultured with and without elevated NEFAs. Among them, 438 genes were upregulated and 575 were downregulated. The differentially expressed genes were enriched in pathways related to metabolism, inflammation, and epithelial-mesenchymal transition. Conclusions The pathways and upstream regulators suggested that the cocultured GCs responded to the elevated NEFAs with (1) inhibition of the transition from granulosa to luteal cell, (2) interactions of metabolism change, anti-inflammation, mitochondrial function, and cell transition, (3) intercommunication with cocultured COCs of anti-inflammatory factors.

scholarly journals Effect and Mechanism of TL1A Expression on Epithelial-Mesenchymal Transition during Chronic Colitis-Related Intestinal Fibrosis

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Jia Wenxiu ◽  
Yang Mingyue ◽  
Han Fei ◽  
Luo Yuxin ◽  
Wu Mengyao ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Tumor Necrosis ◽  
Epithelial To Mesenchymal Transition ◽  
Intestinal Inflammation ◽  
Epithelial Mesenchymal Transition ◽  
Lymphoid Cells ◽  
Inflammatory Factors ◽  
Mesenchymal Transition ◽  
Intestinal Fibrosis

Background and Aims. Recent evidences reveal that epithelial to mesenchymal transition (EMT) exacerbates the process of intestinal fibrosis. Tumor necrosis factor-like ligand 1A (TL1A) is a member of the tumor necrosis family (TNF), which can take part in the development of colonic inflammation and fibrosis by regulating immune response or inflammatory factors. The purpose of this study was to elucidate the possible contribution of TL1A in onset and progression of intestinal inflammation and fibrosis through EMT. Methods. Colonic specimens were obtained from patients with inflammatory bowel disease (IBD) and control individuals. The expression levels of TL1A and EMT-related markers in intestinal tissues were evaluated. Furthermore, the human colorectal adenocarcinoma cell line, HT-29, was stimulated with TL1A, anti-TL1A antibody, or BMP-7 to assess EMT process. In addition, transgenic mice expressing high levels of TL1A in lymphoid cells were used to further investigate the mechanism of TL1A in intestinal fibrosis. Results. High levels of TL1A expression were detected in the intestinal specimens of patients with ulcerative colitis and Crohn’s disease and were negatively associated with the expression of an epithelial marker (E-cadherin), while it was positively associated with the expression of interstitial markers (FSP1 and α-SMA). Transgenic mice with high expression of TL1A were more sensitive to dextran sodium sulfate and exhibited severe intestinal inflammation and fibrosis. Additionally, the TGF-β1/Smad3 pathway may be involved in TL1A-induced EMT, and the expression of IL-13 and EMT-related transcriptional molecules (e.g., ZEB1 and Snail1) was increased in the intestinal specimens of the transgenic mice. Furthermore, TL1A-induced EMT can be influenced by anti-TL1A antibody or BMP-7 in vitro. Conclusions. TL1A participates in the formation and process of EMT in intestinal fibrosis. This new knowledge enables us to better understand the pathogenesis of intestinal fibrosis and identify new therapeutic targets for its treatment.

Effects of non-esterified fatty acids on bovine granulosa cells and developmental potential of oocytes in vitro

2004 ◽  
Vol 81 (3-4) ◽  
pp. 225-235 ◽  
Author(s):  
R Jorritsma ◽  
M.L César ◽  
J.T Hermans ◽  
C.L.J.J Kruitwagen ◽  
P.L.A.M Vos ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Granulosa Cells ◽  
Developmental Potential ◽  
Esterified Fatty Acids

scholarly journals Long non-coding RNA PGM5-AS1 modulates epithelial-mesenchymal transition and invasion and metastasis of osteosarcoma cells by impairing miR-140-5p-mediated FBN1 inhibition

2019 ◽  
Author(s):  
Wei Liu ◽  
Pengcheng Liu ◽  
Hang Gao ◽  
Xu Wang ◽  
Ming Yan
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Differentially Expressed ◽  
Luciferase Reporter ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Luciferase Reporter Gene ◽  
Mesenchymal Transition ◽  
Therapeutic Modalities ◽  
Gene Assay

Abstract Background Osteosarcoma represents a uncommon tumor occurring in bone possessing elevated rate of incidence and reduced rate of healing. Hence, developing effective therapeutic modalities to treat osteosarcoma is essential. Various long non-coding RNAs (lncRNAs) are engaged in prognostic and diagnostic processes of diseases. Thus, we identified the molecular mechanism of lncRNA PGM5-AS1 in progression of osteosarcoma.Methods Microarray-based analysis was employed to screen the osteosarcoma-related differentially expressed lncRNA. PGM5-AS1 level in osteosarcoma tissues and cells as well as the levels of microRNA-140-5p (miR-140-5p) and fibrillin-1 (FBN1) in osteosarcoma tissues were determined. Dual-luciferase reporter gene assay, RNA pull-down assay, and RNA immunoprecipitation assay were done to find out the relation among PGM5-AS1, miR-140-5p, and FBN1. shRNA, mimic, or inhibitor was applied to alter the levels of PGM5-AS1, miR-140-5p, and FBN1 in osteosarcoma cells to investigate how they regulated migration, invasion, and epithelial-mesenchymal transition (EMT) of osteosarcoma cells in vitro. The nude mice were injected with osteosarcoma cell line with depleted PGM5-AS1 to detect the role of PGM5-AS1 in tumorigenesis in vivo.Results PGM5-AS1 possessing elevated level in osteosarcoma was identified as the differentially expressed lncRNA in osteosarcoma. Osteosarcoma tissues exhibited low miR-140-5p expression and high FBN1 expression. Results confirmed that PGM5-AS competitively bound to miR-140-5p to upregulate FBN1. Also, hindering PGM5-AS1 and FBN1 or enforcing miR-140-5p dampened migration, invasion, and EMT of osteosarcoma cells in vitro. Furthermore, silencing PGM5-AS1 markedly inhibited tumorigenesis in vivo.Conclusion All in all, PGM5-AS1 depletion causes FBN1 reduction to retard osteosarcoma processes by negatively modulating miR-140-5p, highlighting PGM5-AS1 silencing as a biomarker for osteosarcoma management.

scholarly journals MicroRNA-144 Suppresses Prostate Cancer Growth and Metastasis by Targeting EZH2

2021 ◽  
Vol 20 ◽  
pp. 153303382198981
Author(s):  
Xin-bo Sun ◽  
Yong-wei Chen ◽  
Qi-sheng Yao ◽  
Xu-hua Chen ◽  
Min He ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
Proliferation And Apoptosis ◽  
High Incidence ◽  
Inhibit Cell Proliferation

Background: Prostate cancer is a common malignant tumor with a high incidence. MicroRNAs (miRNAs) have been shown to be important post-transcriptional regulators during tumorigenesis. This study aimed to explore the effect of miR-144 on PCa proliferation and apoptosis. Material and Methods: The expression of miR-144 and EZH2 were examined in clinical PCa tissues. PCa cell line LNCAP and DU-145 was employed and transfected with miR-144 mimics or inhibitors. The correlation between miR-144 and EZH2 was verified by luciferase reporter assay. Cell viability, apoptosis and migratory capacity were detected by CCK-8, flow cytometry assay and wound healing assay. The protein level of EZH2, E-Cadherin, N-Cadherin and vimentin were analyzed by western blotting. Results: miR-144 was found to be negatively correlated to the expression of EZH2 in PCa tissues. Further studies identified EZH2 as a direct target of miR-144. Moreover, overexpression of miR-144 downregulated expression of EZH2, reduced cell viability and promoted cell apoptosis, while knockdown of miR-144 led to an inverse result. miR-144 also suppressed epithelial-mesenchymal transition level of PCa cells. Conclusion: Our study indicated that miR-144 negatively regulate the expression of EZH2 in clinical specimens and in vitro. miR-144 can inhibit cell proliferation and induce cell apoptosis in PCa cells. Therefore, miR-144 has the potential to be used as a biomarker for predicting the progression of PCa.

scholarly journals Overexpressed P75CUX1 promotes EMT in glioma infiltration by activating β-catenin

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Anqi Xu ◽  
Xizhao Wang ◽  
Jie Luo ◽  
Mingfeng Zhou ◽  
Renhui Yi ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Tumor Grade ◽  
Prognostic Indicator ◽  
Migration And Invasion ◽  
Poor Overall Survival ◽  
Mesenchymal Transition ◽  
Kaplan Meier ◽  
Homeobox Protein

AbstractThe homeobox protein cut-like 1 (CUX1) comprises three isoforms and has been shown to be involved in the development of various types of malignancies. However, the expression and role of the CUX1 isoforms in glioma remain unclear. Herein, we first identified that P75CUX1 isoform exhibited consistent expression among three isoforms in glioma with specifically designed antibodies to identify all CUX1 isoforms. Moreover, a significantly higher expression of P75CUX1 was found in glioma compared with non-tumor brain (NB) tissues, analyzed with western blot and immunohistochemistry, and the expression level of P75CUX1 was positively associated with tumor grade. In addition, Kaplan–Meier survival analysis indicated that P75CUX1 could serve as an independent prognostic indicator to identify glioma patients with poor overall survival. Furthermore, CUX1 knockdown suppressed migration and invasion of glioma cells both in vitro and in vivo. Mechanistically, this study found that P75CUX1 regulated epithelial–mesenchymal transition (EMT) process mediated via β-catenin, and CUX1/β-catenin/EMT is a novel signaling cascade mediating the infiltration of glioma. Besides, CUX1 was verified to promote the progression of glioma via multiple other signaling pathways, such as Hippo and PI3K/AKT. In conclusion, we suggested that P75CUX1 could serve as a potential prognostic indicator as well as a novel treatment target in malignant glioma.

scholarly journals Effect of PACAP on Hypoxia-Induced Angiogenesis and Epithelial–Mesenchymal Transition in Glioblastoma

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 965
Author(s):  
Grazia Maugeri ◽  
Agata Grazia D’Amico ◽  
Salvatore Saccone ◽  
Concetta Federico ◽  
Daniela Maria Rasà ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Matrix Metalloproteinase 2 ◽  
Mesenchymal Transition ◽  
Hypoxic Area ◽  
Vitro Model ◽  
Human Gbm ◽  
Endothelial Growth Factor

Pituitary adenylate cyclase-activating polypeptide (PACAP) exerts different effects in various human cancer. In glioblastoma (GBM), PACAP has been shown to interfere with the hypoxic micro-environment through the modulation of hypoxia-inducible factors via PI3K/AKT and MAPK/ERK pathways inhibition. Considering that hypoxic tumor micro-environment is strictly linked to angiogenesis and Epithelial–Mesenchymal transition (EMT), in the present study, we have investigated the ability of PACAP to regulate these events. Results have demonstrated that PACAP and its related receptor, PAC1R, are expressed in hypoxic area of human GBM colocalizing either in epithelial or mesenchymal cells. By using an in vitro model of GBM cells, we have observed that PACAP interferes with hypoxic/angiogenic pathway by reducing vascular-endothelial growth factor (VEGF) release and inhibiting formation of vessel-like structures in H5V endothelial cells cultured with GBM-conditioned medium. Moreover, PACAP treatment decreased the expression of mesenchymal markers such as vimentin, matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) as well as CD44 in GBM cells by affecting their invasiveness. In conclusion, our study provides new insights regarding the multimodal role of PACAP in GBM malignancy.

scholarly journals A novel homeostatic loop of sorcin drives paclitaxel-resistance and malignant progression via Smad4/ZEB1/miR-142-5p in human ovarian cancer

Oncogene ◽  
2021 ◽  
Author(s):  
Jinguo Zhang ◽  
Wencai Guan ◽  
Xiaolin Xu ◽  
Fanchen Wang ◽  
Xin Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Calcium Binding ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Progression ◽  
Bioinformatics Analyses ◽  
Aberrant Expression ◽  
Mesenchymal Transition ◽  
E Box

AbstractThe primary chemotherapy of ovarian cancer (OC) often acquires chemoresistance. Sorcin (SRI), a soluble resistance-related calcium-binding protein, has been reported to be an oncogenic protein in cancer. However, the molecular mechanisms of SRI regulation and the role and aberrant expression of SRI in chemoresistant OC remain unclear. Here, we identified SRI as a key driver of paclitaxel (PTX)-resistance and explored its regulatory mechanism. Using transcriptome profiles, qRT-PCR, proteomics, Western blot, immunohistochemistry, and bioinformatics analyses, we found that SRI was overexpressed in PTX-resistant OC cells and the overexpression of SRI was related to the poor prognosis of patients. SRI was a key molecule required for growth, migration, and PTX-resistance in vitro and in vivo and was involved in epithelial–mesenchymal transition (EMT) and stemness. Mechanistic studies showed that miR-142-5p directly bound to the 3ʹ-UTR of SRI to suppress its expression, whereas a transcription factor zinc-finger E-box binding homeobox 1 (ZEB1) inhibited the transcription of miR-142-5p by directly binding to the E-box fragment in the miR-142 promoter region. Furthermore, ZEB1 was negatively regulated by SRI which physically interacted with Smad4 to block its translocation from the cytosol to the nucleus. Taken together, our findings unveil a novel homeostatic loop of SRI that drives the PTX-resistance and malignant progression via Smad4/ZEB1/miR-142-5p in human OC. Targeting this SRI/Smad4/ZEB1/miR-142-5p loop may reverse the PTX-resistance.

YAP1 Overexpression Is Associated with Kidney Dysfunction in Lupus Nephritis

Pathobiology ◽  
2021 ◽  
pp. 1-12
Author(s):  
Ying Xie ◽  
Yuanyuan Ruan ◽  
Huimei Zou ◽  
Yixin Wang ◽  
Xin Wu ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Epithelial Mesenchymal Transition ◽  
Kidney Tissue ◽  
Mouse Kidney ◽  
Experimental Comparison ◽  
Control Group ◽  
Mrna Levels ◽  
Mesenchymal Transition ◽  
Protein Levels

<b><i>Objective:</i></b> The goal of the present study was to determine the expression of yes-associated protein 1 (YAP1) in renal tissues of mice with lupus nephritis (LN) and elucidate its role in the progression of renal fibrosis. <b><i>Methods:</i></b> C57BL/6 mice and MRL/lpr mice were selected for experimental comparison. Mouse kidney tissues were removed and sectioned for hematoxylin and eosin staining, Masson’s trichome staining, Sirius staining, and immunohistochemistry. The mRNA and protein levels of YAP1 in mouse kidney tissues were detected, and the correlation between YAP1 and fibronectin (FN) mRNA levels was analyzed. Mouse renal epithelial cells were used for in vitro experiments. After transfection and stimulation, the cells were divided into 4 groups, namely the C57BL/6 serum group (group 1), the MRL/lpr serum group (group 2), the MRL/lpr serum + siRNA-negative control group (group 3), and the MRL/lpr serum + siRNA-YAP1 group (group 4). Epithelial-mesenchymal transition (EMT) markers in each group were detected by Western blotting and immunofluorescence staining. Serum creatinine, blood urea nitrogen, and urinary protein levels were detected and assessed for their correlation with YAP1 mRNA levels by Spearman’s analysis. <b><i>Results:</i></b> Compared to C57BL/6 mice, MRL/lpr mice exhibited obvious changes in fibrosis in renal tissues. In addition, YAP1 expression was significantly higher in the renal tissues of MRL/lpr mice than in those of C57BL/6 mice, and YAP1 mRNA levels were positively correlated with those of FN. YAP1 silencing in lupus serum-stimulated cells could effectively relieve serum-induced EMT. Finally, we observed that YAP1 mRNA levels in mouse kidney tissue were significantly and positively correlated with the degree of renal function injury. <b><i>Conclusion:</i></b> YAP1 expression in the kidney tissues of LN mice was higher than that observed in normal mice, indicating that YAP1 may play an important role in the occurrence and development of LN.

scholarly journals Long noncoding RNA LINC00941 promotes pancreatic cancer progression by competitively binding miR-335-5p to regulate ROCK1-mediated LIMK1/Cofilin-1 signaling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jie Wang ◽  
Zhiwei He ◽  
Jian Xu ◽  
Peng Chen ◽  
Jianxin Jiang
Keyword(s):  
Pancreatic Cancer ◽  
Cell Growth ◽  
Cell Lines ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Loss Of Function ◽  
Mesenchymal Transition

AbstractAn accumulation of evidence indicates that long noncoding RNAs are involved in the tumorigenesis and progression of pancreatic cancer (PC). In this study, we investigated the functions and molecular mechanism of action of LINC00941 in PC. Quantitative PCR was used to examine the expression of LINC00941 and miR-335-5p in PC tissues and cell lines, and to investigate the correlation between LINC00941 expression and clinicopathological features. Plasmid vectors or lentiviruses were used to manipulate the expression of LINC00941, miR-335-5p, and ROCK1 in PC cell lines. Gain or loss-of-function assays and mechanistic assays were employed to verify the roles of LINC00941, miR-335-5p, and ROCK1 in PC cell growth and metastasis, both in vivo and in vitro. LINC00941 and ROCK1 were found to be highly expressed in PC, while miR-335-5p exhibited low expression. High LINC00941 expression was strongly associated with larger tumor size, lymph node metastasis, and poor prognosis. Functional experiments revealed that LINC00941 silencing significantly suppressed PC cell growth, metastasis and epithelial–mesenchymal transition. LINC00941 functioned as a molecular sponge for miR-335-5p, and a competitive endogenous RNA (ceRNA) for ROCK1, promoting ROCK1 upregulation, and LIMK1/Cofilin-1 pathway activation. Our observations lead us to conclude that LINC00941 functions as an oncogene in PC progression, behaving as a ceRNA for miR-335-5p binding. LINC00941 may therefore have potential utility as a diagnostic and treatment target in this disease.

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