scholarly journals Modulation of Tumor Microenvironment through Aurea Helianthus Extract and Induced Exosomes

2020 ◽  
Author(s):  
Yoonjin Park ◽  
Kyunghwa Lee ◽  
Suhng Wook Kim ◽  
Min woo Lee ◽  
Boyong Kim ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Tumor Microenvironment ◽  
Mitochondrial Membrane ◽  
Drug Susceptibility ◽  
Migration And Invasion ◽  
Fallopian Tubes ◽  
Biological Drug ◽  
Ec Cells ◽  
Cellular Types ◽  
Cancer Activity

Abstract Endometrial cancer (EC) cells metastasize to various regions, including ovaries, fallopian tubes, cervix, blood, liver, bone, and brain. Various carcinogens cause EC. Exosomes are released from several types of cells and contain different components depending on cellular types. Although tocopherol- α and rutin were high components in Aurea helianthus, the Aurea elianthus extract was enormously useful in modulating tumor microenvironment contrasted to the two substances. Notably, we established that the extract induced bioactive exosomes in EC cells, and profiling of miRNAs in the extract inducing exosomes (EIE) present potency to develop a biological drug. The extract and EIE contributed to the following five biological categories for EC cells: (1) suppressed migration and invasion; (2) activated cellular senescence by attenuating mitochondrial membrane potential and enhancing autophagy; (3) attenuated eproductive cancer activity; (4) activated drug susceptibility; and (5) EIE contained miRNA associated with decreasing inflammation.

scholarly journals Effects of Induced Exosomes from Endometrial Cancer Cells on Tumor Activity in the Presence of Aurea helianthus Extract

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2207
Author(s):  
Yoonjin Park ◽  
Kyunghwa Lee ◽  
Suhng Wook Kim ◽  
Min Woo Lee ◽  
Boyong Kim ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cell Migration ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Cellular Senescence ◽  
Mitochondrial Membrane ◽  
Drug Susceptibility ◽  
Migration And Invasion ◽  
Ec Cells ◽  
Cancer Activity

Endometrial cancer (EC) cells metastasize to various regions, including the ovaries, fallopian tubes, cervix, blood, liver, bone, and brain. Various carcinogens are known to cause EC. Exosomes are released from several types of cells and contain various cellular components. In this study, flow cytometry and quantitative PCR were used to evaluate marker levels, cell migration, cell invasion, and mitochondrial membrane potential, and cellular senescence tests were used to estimate cancer activity. The microRNAs were profiled using next-generation sequencing. Although tocopherol-α and rutin content in Aurea helianthus is high, A. helianthus extract was more useful in modulating tumor activity compared to the two aforementioned substances. Notably, we established that the extract induced bioactive exosomes in EC cells, and profiling of miRNAs in the extract-inducing exosomes (EIE) indicated their potency to be developed as a biological drug. The extract and EIE contributed to the following five biological process categories for EC cells: (1) cell migration and invasion suppression, (2) cellular senescence activation by attenuating mitochondrial membrane potential and enhancing autophagy, (3) reproductive cancer activity attenuation, (4) drug susceptibility activation, and (5) EIE containing miRNAs associated with decreasing inflammation.

scholarly journals Long noncoding RNA SNHG25 promotes the malignancy of endometrial cancer by sponging microRNA-497-5p and increasing FASN expression

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yuhua He ◽  
Shuifang Xu ◽  
Yi Qi ◽  
Jinfang Tian ◽  
Fengying Xu
Keyword(s):  
Endometrial Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Fatty Acid Synthase ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Study Cohort ◽  
Loss Of Function ◽  
Ec Cells

Abstract Background Small nucleolar RNA host gene 25 (SNHG25), a long noncoding RNA, has been well-studied in epithelial ovarian cancer. However, the specific functions of SNHG25 in endometrial cancer (EC) have not been studied yet. In this study, we aimed to elucidate the clinical significance of SNHG25 in EC and determine the regulatory activity of SNHG25 on the tumor-associated EC phenotype. We also thoroughly explored the molecular mechanisms underlying SNHG25 function in EC. Methods Gene expression was measured using quantitative real-time polymerase chain reaction. The detailed functions of SNHG25 in EC were examined by performing loss-of-function experiments. Moreover, the regulatory mechanisms involving SNHG25, microRNA-497-5p, and fatty acid synthase (FASN) were unveiled using the luciferase reporter assay and RNA immunoprecipitation. Results We observed a high level of SNHG25 in EC using the TCGA dataset and our study cohort. Patients with a high SNHG25 level had shorter overall survival than those with a low SNHG25 level. SNHG25 deficiency resulted in tumor-repressing activities in EC cells by decreasing cell proliferation, migration, and invasion and promoting cell apoptosis. Furthermore, the function of SNHG25 depletion in impairing tumor growth in vivo was confirmed. SNHG25 sequestered miR-497-5p as a competing endogenous RNA in EC and consequently positively regulated FASN expression. Thus, the decrease in miR-497-5p or increase in FASN could neutralize the modulatory actions of SNHG25 knockdown in EC cells. Conclusions The depletion of SNHG25 impedes the oncogenicity of EC by targeting the miR-497-5p/FASN axis. The newly elucidated SNHG25/miR-497-5p/FASN pathway may be a promising target for the molecular-targeted management of EC.

scholarly journals Long Non-coding RNA SNHG25 Promotes the Malignancy of Endometrial Cancer by Sponging microRNA-497-5p and Thereby Increasing FASN Expression

2021 ◽  
Author(s):  
Yuhua He ◽  
Shuifang Xu ◽  
Yi Qi ◽  
Jinfang Tian ◽  
Fengying Xu
Keyword(s):  
Endometrial Cancer ◽  
Noncoding Rna ◽  
Fatty Acid Synthase ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Molecular Events ◽  
Ec Cells ◽  
High Level

Abstract BackgroundSmall nucleolar RNA host gene 25 (SNHG25), a long-noncoding RNA, has been well studied in epithelial ovarian cancer. Yet, the specific functions of SNHG25 in endometrial cancer (EC) have not been researched. In this study, we proposed to expose the clinic significance of SNHG25 in EC, and then unravel the regulatory activity of SNHG25 on the tumor-associated phenotype of EC. More interestingly, the possible molecular events occurred when SNHG25 executives its function in EC were explored thoroughly. MethodsWe measured genes expression applying quantitative real-time polymerase chain reaction. The detailed functions of SNHG25 in EC were examined employing loss-of-function experiments. What’s more, we unveiled the regulatory mechanisms among SNHG25, microRNA-497-5p and fatty acid synthase (FASN) with the application of luciferase reporter assay and RNA Immunoprecipitation. ResultsWe verified a high level of SNHG25 in EC through TCGA dataset and our own cohort. Patients with a high SNHG25 level featured shorter overall survival in contrast to patients with a low SNHG25 level. SNHG25 deficient caused tumor-repressing actions in EC cells by decreasing cell proliferation, migration and invasion and promoting cell apoptosis. Furthermore, we certified the function of SNHG25 depletion in impairing tumor growth in vivo. With respect to the mechanisms, SNHG25 sequestered miR-497-5p as a competing endogenous RNA in EC and consequently positively regulated FASN expression. Striking, the decrease of miR-497-5p or increase of FASN could neutralize the modulatory actions of SNHG25 knockdown in EC cells. ConclusionsDepleted SNHG25 hampered the oncogenicity of EC by targeting miR-497-5p/FASN axis. The newly certified SNHG25/miR-497-5p/FASN pathway may potentially have usefulness as a promising target for molecular targeted management.

scholarly journals Exploring lncRNA-Mediated Regulatory Networks in Endometrial Cancer Cells and the Tumor Microenvironment: Advances and Challenges

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 234 ◽  
Author(s):  
Peixin Dong ◽  
Ying Xiong ◽  
Junming Yue ◽  
Sharon J. B. Hanley ◽  
Noriko Kobayashi ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Tumor Microenvironment ◽  
Signaling Pathways ◽  
Regulatory Networks ◽  
Myometrial Invasion ◽  
Tumor Grade ◽  
Figo Stage ◽  
Normal Tissues ◽  
P53 Signaling ◽  
Ec Cells

Recent studies have revealed both the promise and challenges of targeting long non-coding RNAs (lncRNAs) to diagnose and treat endometrial cancer (EC). LncRNAs are upregulated or downregulated in ECs compared to normal tissues and their dysregulation has been linked to tumor grade, FIGO stage, the depth of myometrial invasion, lymph node metastasis and patient survival. Tumor suppressive lncRNAs (GAS5, MEG3, FER1L4 and LINC00672) and oncogenic lncRNAs (CCAT2, BANCR, NEAT1, MALAT1, H19 and Linc-RoR) have been identified as upstream modulators or downstream effectors of major signaling pathways influencing EC metastasis, including the PTEN/PI3K/AKT/mTOR, RAS/RAF/MEK/ERK, WNT/β-catenin and p53 signaling pathways. TUG1 and TDRG1 stimulate the VEGF-A pathway. PCGEM1 is implicated in activating the JAK/STAT3 pathway. Here, we present an overview of the expression pattern, prognostic value, biological function of lncRNAs in EC cells and their roles within the tumor microenvironment, focusing on the influence of lncRNAs on established EC-relevant pathways. We also describe the emerging classification of EC subtypes based on their lncRNA signature and discuss the clinical implications of lncRNAs as valuable biomarkers for EC diagnosis and potential targets for EC treatment.

scholarly journals α-bisabolol enhances radiotherapy-induced apoptosis in endometrial cancer cells by reducing the effect of XIAP on inhibiting caspase-3

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Dongmei Fang ◽  
Hongxin Wang ◽  
Min Li ◽  
Wenwen Wei
Keyword(s):  
Endometrial Cancer ◽  
Caspase 3 ◽  
Migration And Invasion ◽  
Inhibitor Of Apoptosis ◽  
Downstream Effectors ◽  
Apoptosis Protein ◽  
Ec Cells ◽  
Cox 2 ◽  
Matrix Metalloproteinases 9 ◽  
Induced Apoptosis

Abstract Endometrial cancer (EC) is one of the most common cancers in females. Although the diagnosis and treatment in early stages can greatly improve the survival rate of patients, the advanced EC still is lethal. Radiotherapy is widely used against EC, and it is a great challenge to find an effective way to overcome the resistance of EC during radiotherapy. α-bisabolol is a promising drug, which has already exhibited its anti-tumor effect in some malignancies. Here we reported that α-bisabolol could inhibit the proliferation of EC cells. It is also shown that their abilities of migration and invasion were effectively reduced by α-bisabolol. Furthermore, our results also demonstrated that α-bisabolol could improve sensitivity of EC cells in radiotherapy and further inhibited the growth of EC cells. By Western blot, we found the expression of matrix metalloproteinases-9 (MMP-9) and cyclin E were significantly decreased, which indicated that EC cells can be further suppressed by using α-bisabolol and radiotherapy. It is also demonstrated in our study that the rate of apoptotic cells is markedly increased in EC by using these two treatments. The significant decrease in X-linked inhibitor of apoptosis protein (XIAP) and increase in caspase-3 detected in our study suggested that the enhancement of apoptosis is mediated by XIAP/caspase-3 pathway, which was further confirmed by examining the downstream effectors of caspase-3, COX-2, PARP and cleaved PARP. In the present study, we demonstrated that α-bisabolol could enhance the sensitivity of EC cells to radiotherapy, which provide a novel alternative for overcoming radioresistance of EC cells and achieving a better outcome in radiotherapy.

E74-Like Factor 3 Promotes Endometrial Cancer Cell Proliferation, Migration and Invasion via Regulating Mucin 1/Hypoxia-Inducible Factor 1α Pathway

2022 ◽  
Vol 12 (5) ◽  
pp. 926-932
Author(s):  
Xin Guan ◽  
Ning Sun
Keyword(s):  
Cell Proliferation ◽  
Endometrial Cancer ◽  
Western Blot ◽  
Cell Lines ◽  
Hypoxia Inducible Factor ◽  
Migration And Invasion ◽  
Mucin 1 ◽  
Positive Correlation ◽  
Ec Cells ◽  
High Level

High expression of E74-like factor 3 (ELF3) has been reported in type 1 endometrial cancer (EC). Bioinformatics analysis predicted a positive correlation with ELF3 and mucin 1 (MUC1)/hypoxiainducible factor 1α (HIF-1α), a previously identified cancer-promoting pathway. This study focused on the MUC1/HIF-1α-involved action mechanism of ELF3 in EC. ELF3 expression in EC cell lines was measured by RT-qPCR and western blot analysis. Following the expression of ELF3 was silent, cell proliferation was examined using CCK-8 and colony formation assay, cell migration and invasion were observed using wound healing and transwell assays. The effect of ELF1 silencing on MUC1/HIF-1α expression was detected by western blot. Rescue experiments incorporating pcDNA3.1(+)/MUC1 explored the interaction between ELF3 and MUC1/HIF-1α in EC cell proliferation, migration and invasion. ELF3 was found to be expressed at a high level in EC cell lines, and the silencing of it effectively inhibited EC cell proliferation. Moreover, ELF silencing also inhibited the migration and invasion of EC cells. Consistent with the database prediction, a positive correlation between ELF3 and MUC1/HIF-1α was observed. More importantly, MUC1 overexpression abated the promotive effect of ELF3 silencing on EC cell proliferation, migration and invasion. ELF3 promotes EC cell proliferation, migration and invasion by regulating MUC1/HIF-1α pathway. Thus, ELF3 as well as MUC1/HIF-1α pathway may be particle targets in the treatment of EC.

scholarly journals miR-29a-3p inhibits endometrial cancer cell proliferation, migration and invasion by targeting VEGFA/CD C42/PAK1

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Aizhi Geng ◽  
Lin Luo ◽  
Fengyun Ren ◽  
Ling Zhang ◽  
Haiying Zhou ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Signaling Pathway ◽  
Scratch Test ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation ◽  
Ec Cells ◽  
Formation Experiment

Abstract Background This study aimed to investigate the mechanism of miR-29a-3p in regulating endometrial cancer (EC) progression. Methods A total of 72 EC patients were enrolled. EC cells were transfected. Cells proliferation, cloning ability, migration and invasion were researched by MTT assay, colony formation experiment, cell scratch test and Transwell experiment respectively. Dual-luciferase reporter assay was performed. Xenograft experiment was conducted using nude mice. miR-29a-3p, VEGFA, CDC42, PAK1 and p-PAK1 expression in cells/tissues was investigated by qRT-PCR and Western blot. Results miR-29a-3p expression was aberrantly reduced in EC patients, which was associated with poor outcome. miR-29a-3p inhibited EC cells proliferation, cloning formation, migration and invasion (P <  0.05 or P <  0.01 or P <  0.001). miR-29a-3p inhibited CDC42/PAK1 signaling pathway activity in EC cells (P <  0.01). VEGFA expression was directly inhibited by miR-29a-3p. miR-29a-3p suppressed EC cells malignant phenotype in vitro and growth in vivo by targeting VEGFA/CDC42/PAK1 signaling pathway (P < 0.05 or P < 0.01). Conclusion miR-29a-3p inhibits EC cells proliferation, migration and invasion by targeting VEGFA/CDC42/PAK1 signaling pathway.

scholarly journals lncRNA SNHG5 Modulates Endometrial Cancer Progression via the miR-25-3p/BTG2 Axis

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Shi Li ◽  
Yanan Shan ◽  
Xiaoya Li ◽  
Cong Zhang ◽  
Sisi Wei ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cancer Progression ◽  
Genital Tract ◽  
Noncoding Rna ◽  
Female Genital Tract ◽  
Migration And Invasion ◽  
Putative Target ◽  
Ec Cells ◽  
First Time ◽  
Female Genital

Endometrial carcinoma (EC) is one of the most common malignancies of the female genital tract, although the mechanisms of EC initiation and development remain incompletely understood. In this study, we demonstrated that the noncoding RNA SNHG5 can inhibit the proliferation, migration, and invasion of EC cells by suppressing the expression of its putative target miR-25-3p. Overexpression of miR-25-3p significantly promoted the proliferation, migration, and invasion of EC cells. In addition, we showed that miR-25-3p represses the expression of BTG2 by directly binding to the 3′-UTR of BTG2 mRNA. Furthermore, increased miR-25-3p expression and decreased SNHG5 and BTG2 expression were observed in EC tissues, and the expression of SNHG5 was negatively correlated to that of miR-25-3p but positively correlated to that of BTG2. In summary, for the first time, we report that the SNHG5/miR-25-3p/BTG2 axis plays an important role in EC progression and is of great potential clinical significance for EC diagnosis and therapy.

scholarly journals Kinesin Family Member C1 (KIFC1) Accelerates Proliferation and Invasion of Endometrial Cancer Cells Through Modulating the PI3K/AKT Signaling Pathway

2020 ◽  
Vol 19 ◽  
pp. 153303382096421
Author(s):  
Kening Zhou ◽  
Jian Zhao ◽  
Lifang Qi ◽  
Yingying He ◽  
Jingui Xu ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Family Member ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Ec Cells ◽  
Kinesin Family ◽  
Proliferation And Invasion

Endometrial cancer (EC) is one of the most common cancers among women worldwide. Kinesin family member C1 (KIFC1) has been demonstrated to play crucial roles in various tumors. However, the function of KIFC1 in EC remains to be revealed. In this study, upregulation of KIFC1 expression in human EC tissues was found from analysis on data from The Cancer Genome Atlas (TCGA), and positively correlated with short survival outcome of EC patients. In addition, the mRNA and protein levels of KIFC1 were confirmed to be up-regulated in EC cells (Ishikawa, HEC-1B, HEC-1A and KLE) compared to human normal endometrial stromal cells (hESCs) by quantitative real time PCR and western blot. In vitro functional experiments showed that overexpression of KIFC1 promoted proliferation, migration and invasion of EC cells, while KIFC1 depletion showed the opposite results. Moreover, KIFC1 knockdown suppressed tumor growth in mice. Further mechanism analysis showed that KIFC1 participated in the regulation of EC progression through regulating the PI3K/AKT signaling pathway. Collectively, KIFC1 promoted proliferation and invasion through modulating PI3K/AKT signaling pathway in EC, implying that KIFC1 might provide a promising therapeutic target for the therapy of EC.

scholarly journals circSLC6A6 Sponges miR-497-5p to Promote Endometrial Cancer Progression via the PI4KB/Hedgehog Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Juan Hu ◽  
Xing Peng ◽  
Weina Du ◽  
Yichuan Huang ◽  
Chun Zhang ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cancer Progression ◽  
Hedgehog Pathway ◽  
Luciferase Reporter ◽  
Mechanistic Study ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Ec Cells

Background. As a new kind of noncoding RNAs, circular RNAs (circRNAs) have been substantiated to be involved in multiple biological processes. Accumulating studies indicate that circular RNAs (circRNAs) regulate the development of cancers by acting as miRNA sponges. However, the role of circRNAs in endometrial cancer (EC) is rarely reported. This study was aimed at investigating the functional roles of circSLC6A6 in EC. Methods. The qRT-PCR assay was performed to detect the circSLC6A6 expression in EC tissues and cell lines. The luciferase reporter assay was performed to explore the connection between circSLC6A6 and miR-497-5p as well as the connection between miR-497-5p and PI4KB. The colony formation assay, EdU assay, wound healing assay, and transwell assay were performed to examine the proliferation, migration, and invasion of EC cells. The in vivo assay was performed to reveal the function of circSLC6A6 in tumorigenesis. Results. We found that circSLC6A6 was highly expressed in both EC tissues and cells. And circSLC6A6 promoted the proliferation, migration, and invasion of EC cells in vitro. In vivo, circSLC6A6 promoted tumor growth. Besides, a mechanistic study demonstrated that circSLC6A6 could regulate tumor-associated signaling PI4KB/hedgehog pathway by sponging miR-497-5p. Conclusion. This study illustrates that circSLC6A6 plays a role in promoting EC progression via the miR-497-5p-mediated PI4KB/hedgehog pathway. Our study may provide a potential novel biomarker for EC diagnosis or treatment.

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