Interleukin-27 Inhibits Trophoblast Cell Invasion and Migration by Affecting the Epithelial–Mesenchymal Transition in Preeclampsia

2018 ◽  
Vol 26 (7) ◽  
pp. 928-938 ◽  
Author(s):  
Huisheng Ge ◽  
Nanlin Yin ◽  
Ting-Li Han ◽  
Dongni Huang ◽  
Xuehai Chen ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Trophoblast Cell ◽  
Trophoblast Invasion ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Signal Transducer ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
Epithelial Phenotype ◽  
And Migration

Preeclampsia (PE) is a pregnancy-specific disorder representing a major cause of maternal and perinatal morbidity and mortality. Invasive and migratory phenotypes are acquired by trophoblasts through the process of epithelial–mesenchymal transition (EMT). Studies have shown that trophoblast EMT events are dysregulated in PE and play an important role in its development. Dysregulation of interleukin (IL)-27 and IL-27R (T-cell cytokine receptor (TCCR)/WSX -1) is relevant to PE. In this study, our results demonstrated that IL-27 did not significantly affect the proliferation and apoptosis of HTR -8/SVneo trophoblast cells, while it did significantly inhibit trophoblast invasion and migration. The expression of EMT-related proteins in HTR-8/SVneo cells and extravillous explants was detected after treatment with IL-27. Expression of epithelial markers was increased, and mesenchymal marker expression was reduced. Furthermore, we found that IL-27 could induce significant phosphorylation of Signal Transducer and Activator of Transcription 1 (STAT1) and Signal Transducer and Activator of Transcription 3 (STAT3) in a time-dependent manner in HTR-8/SVneo cells. Selective inhibitors of STAT1 (STAT1 siRNA) and STAT3 (STAT3 siRNA) were used to determine whether both STAT1 and STAT3 are required for IL-27-mediated inhibition of EMT. STAT1 inhibition in IL-27-treated cells attenuated the IL-27 effect, while the inhibition of STAT3 activation had no effect on the development of the epithelial phenotype. These results demonstrate that IL-27 may inhibit trophoblast cell migration and invasion by affecting the EMT process through an STAT1-dominant pathway in PE.

MiR-21 Promotes the Invasion and Metastasis of Gastric Cancer Cells by Activating Epithelial-Mesenchymal Transition

2019 ◽  
Vol 60 (5-6) ◽  
pp. 208-218 ◽  
Author(s):  
Tao Xiao ◽  
Zhigang Jie
Keyword(s):  
Gastric Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
Migration And Invasion ◽  
Epithelial Cell Line ◽  
Invasion And Metastasis ◽  
Gastric Cancer Cells ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration

Background: Gastric cancer (GC) is one of the most common malignant tumors. It is likely to occur in lymph nodes and is prone to distant metastasis in its early stages, which portends a poor prognosis. Previous studies have shown that miRNA-21 was abnormally highly expressed and associated with early metastasis in GC, but the mechanism by which it regulates the invasion and metastasis of GC has not been elucidated. Methods: Epithelial-mesenchymal transition (EMT) is an important pathologic basis of tumor invasion and metastasis, and in this study, the relationship between miRNA-21 and EMT in GC invasion and metastasis was investigated using RT-qPCR, Western blot, and wound scratch and transwell assays. Results: We found that miRNA-21 expression in GC cell lines was higher than in a gastric mucosal epithelial cell line. After transfection with an miRNA-21 mimic, the upregulation of EMT was found to promote migration and invasion of MGC-803 cells. However, the downregulation of EMT was found to accompany the inhibition of invasion and migration of GC cells after downregulation of miRNA-21 expression due to the transfection of an miRNA-21 inhibitor. Conclusions: These findings suggest that miRNA-21 might promote the invasion and metastasis of GC by upregulating EMT.

miR-27b-3p Inhibits Invasion, Migration and Epithelial-mesenchymal Transition in Gastric Cancer by Targeting RUNX1 and Activation of the Hippo Signaling Pathway

2021 ◽  
Vol 21 ◽  
Author(s):  
Chen-hui Bao ◽  
Lin Guo
Keyword(s):  
Gastric Cancer ◽  
Target Gene ◽  
Epithelial Mesenchymal Transition ◽  
Hippo Pathway ◽  
Mirna Sequence ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration ◽  
The Hippo Pathway

Background: Gastric cancer (GC) accounts for high mortality, which seriously threatens people’s health. This study set out to probe into the effect and mechanism of miR-27b-3p on invasion and migration of GC. Methods: The miRNA sequence data of GC was acquired from The Cancer Genome Atlas (TCGA) database. The differential expression of miRNAs (DEMis) was acquired through R packages “edgeR” and “limma.” TargetScan, picTar, RNA22, PITA, and miRanda were performed to predict the target gene of miR-27b-3p. Western-blot and RT-PCR were applied to detect the expression level of the selected candidate. Transwell assays evaluated the effect of miR-27b-3p and runt-related transcription factor 1 (RUNX1) on cell migration and invasion. The rescue assay was achieved by co-culture with mimics of miR-27b-3p and vector of RUNX1. The psiCHECK2 vector was used in the luciferase report assay. Results: We found miR-27b-3p was down-regulated in GC and associated with GC patients' poor survival based on the TCGA data and bioinformatics analysis. Furthermore, RUNX1 was the target gene of miR-27b-3p, which was proved by the luciferase report assay. miR-27b-3p and RUNX1 jointly participate in the regulation of the Hippo pathway. The up-regulated miR-27b-3p could inhibit epithelial–mesenchymal transition (EMT) as well as invasion and migration. However, an overexpressed RUNX1 could weaken this phenomenon. Conclusion: miR-27b-3p was down-regulated in GC, and it could regulate the Hippo pathway and affect EMT by inhibiting RUNX1 expression.

Expression of lncRNA TINCR in the placenta of patients with pre-eclampsia and its effect on the biological behaviours of trophoblasts

Zygote ◽  
2021 ◽  
pp. 1-9
Author(s):  
Li Qin ◽  
Qin Yang ◽  
Zhiyi Fei ◽  
Dandan Zhang
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Terminal Differentiation ◽  
S Phase ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Protein Coding ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration ◽  
Related Proteins

Summary To explore the effect of lncRNA TINCR on the biological behaviours of trophoblasts, we detected and analyzed the expression of terminal differentiation-induced non-protein coding RNA (TINCR) in the placenta tissues of pre-eclamptic and non-pre-eclamptic pregnant women. The gain- and loss-of-function of TINCR was performed to examine the proliferation, migration and invasion abilities of Htr-8/Svneo cells. The levels of epithelial–mesenchymal transition (EMT)-related proteins, cyclin and Wnt/β-catenin pathway were detected. High expression of lncRNA TINCR appeared in placental tissues of patients with pre-eclampsia. The proliferation, invasion and migration of Htr-8/Svneo cells were promoted by TINCR downregulation; the cells were transited from G0/G1 to S phase; and EMT was promoted and the Wnt/β-catenin pathway was activated. In summary, the downregulation of lncRNA TINCR activated the Wnt/β-catenin pathway and promoted the proliferation, invasion and migration of Htr-8/Svneo cells. This study may provide a theoretical basis for treatment of patients with pre-eclampsia.

scholarly journals Ethyl pyruvate inhibits glioblastoma cells migration and invasion through modulation of NF-κB and ERK-mediated EMT

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9559
Author(s):  
Qing Huang ◽  
Yongming Fu ◽  
Shan Zhang ◽  
Youxiang Zhang ◽  
Simin Chen ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Ethyl Pyruvate ◽  
Migration And Invasion ◽  
High Recurrence Rate ◽  
Dependent Manner ◽  
Protective Effects ◽  
Glioblastoma Cells ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
U251 Cells

Background Glioblastoma is a grade IV glioma with the highest degree of malignancy and extremely high incidence. Because of the poor therapeutic effect of surgery and radiochemotherapy, glioblastoma has a high recurrence rate and lethality, and is one of the most challenging tumors in the field of oncology. Ethyl pyruvate (EP), a stable lipophilic pyruvic acid derivative, has anti-inflammatory, antioxidant, immunomodulatory and other cellular protective effects. It has been reported that EP has potent anti-tumor effects on many types of tumors, including pancreatic cancer, prostate cancer, liver cancer, gastric cancer. However, whether EP has anti-tumor effect on glioblastoma or not is still unclear. Methods Glioblastoma U87 and U251 cells were treated with different concentrations of EP for 24 h or 48 h. CCK8 assay and Colony-Formation assay were performed to test the viability and proliferation. Wound-healing assay and Transwell assay were carried out to measure cell invasion and migration. Western blot was not only used to detect the protein expression of epithelial-mesenchymal transition (EMT)-related molecules, but also to detect the expression and activation levels of NF-κB (p65) and Extracellular Signal Regulated Kinase (ERK). Results In glioblastoma U87 and U251 cells treated with EP, the viability, proliferation, migration, invasion abilities were inhibited in a dose-dependent manner. EP inhibited EMT and the activation of NF-κB (p65) and ERK. With NF-κB (p65) and ERK activated, EMT, migration and invasion of U87 and U251 cells were promoted. However the activation of NF-κB (p65) and ERK were decreased, EMT, migration and invasion abilities were inhibited in U87 and U251 cells treated with EP. Conclusion EP inhibits glioblastoma cells migration and invasion by blocking NF-κB and ERK-mediated EMT.

Matrix Metalloproteinase (MMP)-12 Promote Invasion and Migration of Esophageal Squamous Cell Carcinoma Cell by Epithelial-Mesenchymal Transition

2019 ◽  
Vol 9 (8) ◽  
pp. 1120-1126
Author(s):  
Dong-Hui Shi ◽  
Jiang Jin
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Matrix Metalloproteinase ◽  
Cell Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
Over Expression ◽  
And Migration

The present study aimed to investigate the role of matrix metalloproteinase (MMP)-12 on cell migration and invasion of esophageal squamous cell carcinoma (ESCC) though epithelial-mesenchymal transition (EMT). The ESCC cell lines (ECA-109, KYSE-30, KYSE-410, KYSE-520) and normal esophageal epithelial cells (HEEC) were cultured. ECA-109 cells were then chosen to be transfected with the plasmids of MMP-12 over-expression, MMP-12 inhibitor, E-cad over-expression and empty control vectors. The protein and mRNA levels of MMP-12 were detected using western blot and qRT-PCR analysis. Transwell and wound healing assays were used to assess cell invasion and migration. Results indicated that MMP-12 was upregulated significantly in all the ESCC cell lines. Overexpression of MMP-12 increased MMP-12 expression, and the abilities of invasion and migration of ECA-109 cells. Overexpression of MMP-12 increased the expression of N-cad and vimentin, but decreased E-cad expression. Additionally, we found that cells treated with inhibitor-MMP-12 were opposite to the above results. Moreover, up-regulation of E-cad were eliminated all effects on ECA-109 cells caused by MMP-12 over-expression. In conclusion, MMP-12 promoted ECA-109 cells migration and invasion by the alteration of the EMT marker protein, which is one of its mechanisms. Therefore, MMP-12 may be a new therapeutic target for ESCC.

scholarly journals Long Noncoding RNA HOST2 Promotes Epithelial-Mesenchymal Transition, Proliferation, Invasion and Migration of Hepatocellular Carcinoma Cells by Activating the JAK2-STAT3 Signaling Pathway

2018 ◽  
Vol 51 (1) ◽  
pp. 301-314 ◽  
Author(s):  
Yang  Wu ◽  
Tan Yuan ◽  
Wei-Wei Wang ◽  
Peng-Lei Ge ◽  
Zhi-Qiang Gao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
And Migration ◽  
E Cadherin

Background/Aims: This study aims to examine the effect of long noncoding RNA HOST2 (LncRNA HOST2) on epithelial-mesenchymal transition (EMT), proliferation, invasion and migration of hepatocellular carcinoma (HCC) cells via activation of the JAK2-STAT3 signaling pathway. Methods: HCC and para-cancerous tissues were collected from 136 HCC patients. Immunohistochemistry was used to detect the expression of JAK2 and STAT3. HCC SMMC7721 cells were grouped into blank, negative control (NC), HOST2 mimic and HOST2 inhibitor groups. The mRNA and protein expression levels of HOST2, JAK2, STAT3, E-cadherin, vimentin, Snail, Slug, Twist and Zeb1 in tissues and cells were determined by reverse transcription -quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. An MTT assay, scratch test and Transwell assay were applied to measure cell proliferation, migration and invasion, respectively. Results: The levels of JAK2, STAT3 and vimentin were higher in HCC tissues, while the expression of E-cadherin was lower in HCC tissues compared with para-cancerous tissues. The silencing of HOST2 significantly decreased cell proliferation, migration and invasion, reduced the levels of HOST2, JAK2, STAT3 and vimentin, and elevated the expression of E-cadherin. HOST2 silencing also decreased the levels of Snail, Slug and Twist but increased the level of Zeb1 protein, while the opposite findings were observed in the HOST2 mimic group. Conclusion: These results reveal a possible mechanism in HCC in which LncRNA HOST2 may increase EMT and enhance proliferation, invasion and metastasis of HCC cells via activation of the JAK2-STAT3 signaling pathway.

scholarly journals The m6A methyltransferase METTL3 controls epithelial-mesenchymal transition, migration and invasion of breast cancer through the MALAT1/miR-26b/HMGA2 axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chengpeng Zhao ◽  
Xiaoling Ling ◽  
Yunxia Xia ◽  
Bingxue Yan ◽  
Quanlin Guan
Keyword(s):  
Breast Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
Protein Levels ◽  
Rna Immunoprecipitation ◽  
Functional Relevance ◽  
And Migration

Abstract Background Previous studies have revealed the key functions of N6-methyladenosine (m6A) modification in breast cancer (BC). MALAT1 as a highly m6A modified lncRNA associated with cancer development and metastasis, but the functional relevance of m6A methyltransferase and MALAT1 in BC is still unknown. Here, our study investigated the effects of the novel m6A methyltransferase METTL3 on epithelial-mesenchymal transition (EMT) in BC via the MALAT1/miR-26b/HMGA2 axis. Methods Firstly, we collected clinical BC samples and cultured BC cells, and detected mRNA and protein levels in the human samples and human cell lines by RT-qPCR and Western blot, respectively. Then, the binding of MALAT1 and miR-26b and the targeting relationship between miR-26b and HMGA2 were examined by dual-luciferase assay. Moreover, the binding of MALAT1 and miR-26b was tested by RNA pull down and RNA immunoprecipitation (RIP) assays. Methylated-RNA immunoprecipitation (Me-RIP) was used to detect the m6A modification level of MALAT1. The interaction of METTL3 and MALAT1 was detected by photoactivatable ribonucleoside-crosslinking immunoprecipitation (PAR-CLIP). Finally, effects on invasion and migration were detected by Transwell. Results In BC, the level of miR-26b was consistently low, while the levels of METTL3, MALAT1 and HMGA2 were high. Further experiments showed that METTL3 up-regulated MALAT1 expression by modulating the m6A modification of MALAT1, and that MALAT1 could promote the expression of HMGA2 by sponging miR-26b. In BC cells, we found that silencing METTL3 could inhibit EMT and tumor cell invasion by suppressing MALAT1. Furthermore, MALAT1 mediated miR-26b to target HMGA2 and promote EMT, migration, and invasion. In summary, METTL3 promoted tumorigenesis of BC via the MALAT1/miR-26b/HMGA2 axis. Conclusions Silencing METTL3 down-regulate MALAT1 and HMGA2 by sponging miR-26b, and finally inhibit EMT, migration and invasion in BC, providing a theoretical basis for clinical treatment of BC.

scholarly journals Inhibition on JNK Mimics Silencing of Wnt-11 Mediated Cellular Response in Androgen-Independent Prostate Cancer Cells

Biology ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 142
Author(s):  
Elif Damla Arisan ◽  
Ozge Rencuzogullari ◽  
Buse Keskin ◽  
Guy H. Grant ◽  
Pinar Uysal-Onganer
Keyword(s):  
Prostate Cancer ◽  
Cellular Response ◽  
Kinase Inhibitor ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Cellular Functions ◽  
Jnk Pathway ◽  
Mesenchymal Transition ◽  
And Migration

Prostate cancer (PCa) is one of the most common cancers among men, and one of the leading causes of cancer death for men. The c-Jun N-terminal kinase (JNK) pathway is required for several cellular functions, such as survival, proliferation, differentiation, and migration. Wnt-11, a member of the Wnt family, has been identified for its upregulation in PCa; however, downstream signalling of Wnt-11 remains to be fully characterized. In this study, we investigated the role of the JNK pathway as a potential downstream factor for Wnt-11 signalling. For this purpose, LNCaP, DU145, and PC-3 PCa cells and normal epithelial PNT1A cells were treated with a specific JNK kinase inhibitor: JNKVIII. Our results showed that JNK inhibition decreased mitochondrial membrane potential and promoted cell death in a cell type-dependent manner. We found that JNK inhibition led to an increase in autophagy and prevented epithelial–mesenchymal transition (EMT) in independently growing androgen cells. JNK inhibition and the silencing of Wnt-11 showed similar responses in DU145 and PC-3 cells and decreased metastasis-related biomarkers, cell migration, and invasion. Overall, our results suggest that JNK signalling plays a significant role in the pathophysiology of PCa by mediating Wnt-11 induced signals. Our data highlights that both the JNK pathway and Wnt-11 could be a useful therapeutic target for the combinatory application of current PCa.

scholarly journals EMT Participates in the Regulation of Exosomes Secretion and Function in Esophageal Cancer Cells

2021 ◽  
Vol 20 ◽  
pp. 153303382110330
Author(s):  
Chuangui Chen ◽  
Zhao Ma ◽  
Hongjing Jiang
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Promoting Effect ◽  
Migration Ability ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration ◽  
And Function ◽  
Esophageal Cancer Cells

Epithelial-mesenchymal transition (EMT) is a key step in tumor invasion and distant metastasis. Abundant evidence has documented that exosomes can mediate EMT of tumor cells and endow them with the ability of invasion and migration. However, there are few studies focusing on whether EMT can reverse the secretion of exosomes. In this study, 2 esophageal cancer cells (FLO-1 and SK-GT-4) were selected to compare the migration ability and EMT activation, and to further analyze the secretion ability of exosomes of the 2 cell lines. According to the results, inhibited activation of EMT in FLO-1 cells with relatively high migration ability could effectively reduce the secretion of exosomes. Besides, in SK-GT-4 cells, EMT activation induced by TGF-β could promote the secretion of exosomes. FLO-1 cell derived exosomes exhibited a paracrine effect of promoting the migration of SK-GT-4 cells, and the use of EMT inhibitors could weaken this ability. Furthermore, inhibition of EMT could change the relative content of some miRNAs in exosomes, with a particularly significant downregulation in the expression of miR-196-5p, miR-21-5p and miR-194-5p. Significantly, artificial transfection of the 3 miRNAs into exosomes by electroporation resulted in the recovery of migration-promoting effect of exosomes. Subsequent experiments further revealed that the effect of EMT on these miRNAs could be explained by the intracellular transcription level or the specific sorting mechanism of exosomes. To sum up, our study undoubtedly reveals that EMT has a regulatory effect on exosomes in the quantity and contents in esophageal cancer cells. Significantly, findings in our study provide experimental evidence for the interaction of EMT with the secretion and sorting pathway of exosomes, and also give a new direction for the further study of tumor metastasis.

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