Exosomal miRNA-215-5p Derived from Adipose-Derived Stem Cells Attenuates Epithelial–Mesenchymal Transition of Podocytes by Inhibiting ZEB2

Background. Podocyte migration is actively involved in the process of podocyte loss and proteinuria production, which is closely associated with the development of diabetic nephropathy (DN). Exosomes from adipose-derived stem cells (ADSCs-Exos) effectively inhibit podocyte apoptosis in the treatment of DN. However, how ADSCs-Exos affect the migration of podocytes is obscure. This study is aimed at exploring the regulatory role of ADSCs-Exos on cell migration and the underlying mechanism. Methods. ADSCs-Exo was authenticated by transmission electron microscopy (TEM), western blotting, and flow cytometry. Cell viability and migration ability of podocytes were measured by CCK8 and Transwell assays, respectively. Relative expressions of miRNAs and mRNAs were determined by qRT-PCR. The transmitting between PKH26-labeled exosome and podocytes was evaluated by IF assay. Dual luciferase reporter assay was employed to detect the relationship between miR-215-5p and ZEB2. Results. The exposure to serum from DN patient (hDN-serum) significantly inhibited cell viability of podocytes, but ADSCs-Exo addition notably blunts cytotoxicity induced by the transient stimulus of hDN-serum. Besides, ADSCs-Exo administration powerfully impeded high glucose- (HG-) induced migration and injury of podocyte. With the podocyte dysfunction, several miRNAs presented a significant decline under the treatment of HG including miR-251-5p, miR-879-5p, miR-3066-5p, and miR-7a-5p, all of which were rescued by the addition of ADSCs-Exo. However, only miR-251-5p was a key determinant in the process of ADSCs-Exo-mediated protective role on podocyte damage. The miR-251-5p inhibitor counteracted the improvement from the ADSCs-Exo preparation on HG-induced proliferation inhibition and migration promotion. Additionally, miR-215-5p mimics alone remarkably reversed HG-induced EMT process of podocyte. Mechanistically, we confirmed that ADSCs-Exos mediated the shuttling of miR-215-5p to podocyte, thereby protecting against HG-induced metastasis, possibly through inhibiting the transcription of ZEB2. Conclusion. ADSCs-Exo has the protective effect on HG-evoked EMT progression of podocytes thru a mechanism involving ZEB2. Potentially, the ADSCs-Exo preparation is a useful therapeutic strategy for improving podocyte dysfunction and DN symptoms clinically.

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LncRNA HOXB-AS3 Promotes Proliferation, Migration, Invasion, and Epithelial-Mesenchymal Transition of Gallbladder Cancer Cells by Activating the MEK/ERK Pathway

10.21203/rs.3.rs-1242836/v1 ◽

2022 ◽

Author(s):

Jiayan Wu ◽

Hongquan Zhu ◽

Jiandong Yu ◽

Zhiping Chen ◽

Zeyu Lin ◽

...

Keyword(s):

Cell Cycle ◽

Cell Migration ◽

Cell Viability ◽

Gallbladder Cancer ◽

Cell Apoptosis ◽

Epithelial Mesenchymal Transition ◽

Underlying Mechanism ◽

Cell Counting ◽

Migration Ability ◽

Mesenchymal Transition

Abstract OBJECTIVE: Long non-coding RNA HOXB-AS3 has been implicated in tumor progression in a variety of carcinomas. However, its biological role in gallbladder cancer (GBC) is unknown. The biological function and underlying mechanism of the lncRNA HOXB-AS3 for GBC were investigated in this study.MATERIALS AND METHODS: To investigate the function of lncRNA HOXB-AS3 in GBC, the level of lncRNA HOXB-AS3 in GBC cells was detected by quantitative reverse-transcription polymerase chain reaction. The cell viability was tested by cell counting kit-8 assay and colony formation assay. Flow cytometry was performed to investigate cell apoptosis and cell cycle. In addition, cell migration ability was assessed by wound healing assay and cell invasion ability by transwell invasion assay. RESULTS: It was found that HOXB-AS3 was obviously elevated in GBC tissues and cells. However, inhibition of HOXB-AS3 could depress NOZ and GBC-SD cell viability as well as induce cell apoptosis. Also, the gallbladder cancer cell cycle was blocked in the G1 phase. Meanwhile, NOZ and GBC-SD cell migration, invasion, and epithelial-mesenchymal transition were obviously suppressed by knockdown of HOXB-AS3. What is more, we found that HOXB-AS3 might promote gallbladder progress by activating the MEK/ERK pathway.CONCLUSION: The results show that lncRNA HOXB-AS3 serves as a key regulator in GBC progression, which provides a new treatment strategy for GBC.

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Bone Morphogenetic Protein 1 Targeting COL1A1 and COL1A2 to Regulate the Epithelial-Mesenchymal Transition Process of Colon Cancer SW620 Cells

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2020.17362 ◽

2020 ◽

Vol 20 (3) ◽

pp. 1366-1374 ◽

Cited By ~ 2

Author(s):

Xijia Zhu ◽

Xishun Luo ◽

Shiyu Jiang ◽

Haipeng Wang

Keyword(s):

Colon Cancer ◽

Cell Viability ◽

Epithelial Mesenchymal Transition ◽

Malignant Tumors ◽

Beta Catenin ◽

Migration Ability ◽

Sw620 Cell ◽

Mesenchymal Transition ◽

Sw620 Cells ◽

And Migration

Epithelial-mesenchymal transition (EMT) is an important factor in promoting the metastasis of colon cancer, which leads to clinical incurability. It has been found that bone morphogenetic proteins (BMPs) are closely related to EMT and the prognoses of most malignant tumors, including colon cancer tumors. However, the effects and mechanisms of BMP1 on the EMT of colon cancer are not yet clear. To explore the effects and mechanisms of BMP1 on the EMT of colon cancer, a BMP1 overexpression plasmid vector was used to interfere with SW620 cells and real-time fluorescence quantitative RNA and western blotting were used to detect the effects of BMP1 on the transcription and translation of COL1A1 and COL1A2 genes, as well as EMT-related genes, including beta-catenin, vimentin, and E-cadherin (E-Cad) genes in SW620 cells. MTT assay and Transwell techniques were used to detect the effects of BMP1 on the proliferation and migration of SW620 cells. The results demonstrate that BMP1 expression in SW620 cells is significantly lower than that in HCoEpiC cells, which promotes the expression of COL1A1 and COL1A2. Additionally, the expression of genes related to EMT, including beta-catenin and vimentin, increased, whereas E-Cad expression decreased. This difference was significant, which led to an increase in cell viability and the number of migrating cells in SW620 cells. Based on the overexpression of BMP1, the expression of COL1A1 and COL1A2 in SW620 was inhibited, which inhibited the process of EMT. Specifically, vimentin expression decreased, and E-Cad and beta-catenin expression increased. Additionally, SW620 cell viability decreased and migration ability decreased. Therefore, it can be concluded that the absence of BMP1 promotes the expression of COL1A and COL1A2 in colon cancer and promotes the process of EMT. Increasing the expression of BMP1 can inhibit the process of EMT in colon cancer, thereby inhibiting the migration of tumors.

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

Technology in Cancer Research & Treatment ◽

10.1177/1533033821989817 ◽

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.

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

Technology in Cancer Research & Treatment ◽

10.1177/15330338211033077 ◽

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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Benzotriazole Enhances Cell Invasive Potency in Endometrial Carcinoma Through CTBP1-Mediated Epithelial-Mesenchymal Transition

Cellular Physiology and Biochemistry ◽

10.1159/000486123 ◽

2017 ◽

Vol 44 (6) ◽

pp. 2357-2367 ◽

Cited By ~ 3

Author(s):

Yiquan Wang ◽

Chencheng Dai ◽

Cheng Zhou ◽

Wenqu Li ◽

Yujia Qian ◽

...

Keyword(s):

Endometrial Carcinoma ◽

Epithelial Mesenchymal Transition ◽

Expression Patterns ◽

Underlying Mechanism ◽

Carcinoma Cells ◽

Mesenchymal Transition ◽

Invasion And Migration ◽

Female Reproductive Health ◽

Gene Microarray Analysis ◽

And Migration

Background/Aims: Benzotriazole (BTR) and its derivatives, such as intermediates and UV stabilizers, are important man-made organic chemicals found in everyday life that have been recently identified as environmental toxins and a threat to female reproductive health. Previous studies have shown that BTR could act as a carcinogen by mimicking estrogen. Environmental estrogen mimics could promote the initiation and development of female cancers, such as endometrial carcinoma, a type of estrogenic-sensitive malignancy. However, there is little information on the relationship between BTR and endometrial carcinoma. In this study, we aimed to demonstrate the biological function of BTR in endometrial carcinoma and explored the underlying mechanism. Methods: The CCK-8 assay was performed to detect cell viability; transwell-filter assay was used to assess cell invasion; gene microarray analysis was employed to determine gene expression patterns in response to BTR treatment; western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were carried out to detect the expression levels of BTR-related genes. Results: Our data showed that BTR could induce the invasion and migration of endometrial carcinoma cells (Ishikawa and HEC-1-B). In addition, BTR increased the expression level of CTBP1, which could enhance the epithelial-mesenchymal transition (EMT) in cancer cells. Moreover, CTBP1 silencing reversed the effect of BTR on EMT progression in endometrial carcinoma cells. Conclusion: This study indicates that BTR could act as a carcinogen to promote the development of endometrial carcinoma mainly through CTBP1-mediated EMT, which deserves more attention.

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Tumor-Suppressive Function of lncRNA-MEG3 in Glioma Cells by Regulating miR-6088/SMARCB1 Axis

BioMed Research International ◽

10.1155/2020/4309161 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15 ◽

Cited By ~ 1

Author(s):

Xin Gong ◽

Meng-Yi Huang

Keyword(s):

Cell Proliferation ◽

Epithelial Mesenchymal Transition ◽

Glioma Cells ◽

Luciferase Reporter ◽

Favorable Effect ◽

Mesenchymal Transition ◽

Gene Assay ◽

And Migration ◽

Proliferation And Migration ◽

Glioma Progression

Objective. Mounting evidence has elaborated the implication of long noncoding RNAs (lncRNAs) in tumorigenesis of several cancers, including glioma. However, little was known about the mechanism of lncRNA maternally expressed gene 3 (MEG3) in the development and progression of glioma. This work is designed to explore the effect of MEG3 on glioma progression and its possible mechanism. Methods. Expressions of lncRNA-MEG3 and SMARCB1 were detected in human glioblastoma U87 and U251 cell lines. Gain and loss of function of MEG3 or/and miR-6088 was performed in U87 and U251 cells to observe its effect on cell proliferation and migration as well as on epithelial-mesenchymal transition (EMT) related markers. Luciferase reporter gene assay was employed to inspect the interactions among MEG3, miR-6088, and SMARCB1. Results. MEG3 and SMARCB1 expressions were downregulated in glioma cells. Transfection of pcDNA3.1-MEG3 or pcDNA3.1-SMARCB1 plasmids could clearly block cell proliferation, migration, and EMT progression. MEG3 functions as a sponge for miR-6088, while SMARCB1 is a downstream protein of miR-6088. Transfection of miR-6088 mimic or si-SMARCB1 could obviously reverse the favorable effect of pcDNA3.1-MEG3 on glioma progression. Conclusion. Collectively, the evidence in this study indicated that MEG3 was downregulated in glioma cells and inhibited proliferation and migration of glioma cells via regulating miR-6088/SMARCB1 axis.

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The effect of hepatic stellate cells on hepatocellular carcinoma progression.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.265 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 265-265

Author(s):

Shuichi Iwahashi ◽

Mitsuo Shimada ◽

Yuji Morine ◽

Satoru Imura ◽

Tetsuya Ikemoto ◽

...

Keyword(s):

Cancer Cells ◽

Cancer Cell ◽

Epithelial Mesenchymal Transition ◽

Stellate Cells ◽

Stem Cell Marker ◽

Cell Marker ◽

Migration Ability ◽

Mesenchymal Transition ◽

And Migration ◽

E Cadherin

265 Background: The hepatic stellate cells (HSCs) localize at the space of Disse in the liver and have multiple functions. They are identified as the major contributor to hepatic fibrosis. Some manuscripts mentioned that activated HSCs predicted prognoses of hepatocellular carcinoma. The aim of this study is to investigate the effect of HSCs and the role of IL-6 / Stat3 pathway on HCC progression. Methods: HCC cells (Hep G2 and Huh 7) were co-cultured with HSC (LX2 and Li90). The viability and migration ability of cancer cells were detected. Also, the expression of epithelial–mesenchymal transition marker (E-cadherin), stem cell marker (EpCAM and CD44), TGF-b and p-STAT3 of cancer cells were evaluated. Then the IL-6 neutralization was performed during HCC cells and HSCs co-culture. The viability and migration ability of cancer cells were detected. Also, the expression of epithelial–mesenchymal transition marker (E-cadherin), stem cell marker (EpCAM and CD44) and p-STAT3 of cancer cells were evaluated. Results: Co-culture with hepatic stellate cell increased cancer cell viability and migration ability. The expression of E-cadherin, EpCAM and CD44 of cancer cells also increased after co-culture with HSCs. The IL-6 expression and secretion of HSCs were elevated by cancer cell stimulation. The over-expressed IL-6 activated STAT3 of cancer cell showed as the level of phosphorylated STAT3 increased. Neutralized IL-6 during co-culture significantly decrease the viability and migration ability of cancer cells. Also, the expression of E-cadherin, EpCAM and CD44 of cancer cells decreased. Conclusions: HSCs might promote HCC progression through IL-6 / STAT3 pathway.

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Upregulating sirtuin 6 ameliorates glycolysis, EMT and distant metastasis of pancreatic adenocarcinoma with krüppel-like factor 10 deficiency

Experimental & Molecular Medicine ◽

10.1038/s12276-021-00687-8 ◽

2021 ◽

Author(s):

Yi-Chih Tsai ◽

Su-Liang Chen ◽

Shu-Ling Peng ◽

Ya-Li Tsai ◽

Zuong-Ming Chang ◽

...

Keyword(s):

Pancreatic Adenocarcinoma ◽

Murine Model ◽

Distant Metastasis ◽

Epithelial Mesenchymal Transition ◽

In Vitro Assays ◽

Migration Ability ◽

Clinical Trial Registration ◽

Mesenchymal Transition ◽

And Migration

AbstractKrüppel-like factor 10 (KLF10) is a tumor suppressor in multiple cancers. In a murine model of spontaneous pancreatic adenocarcinoma (PDAC), additional KLF10 depletion accelerated distant metastasis. However, Klf10 knockout mice, which suffer from metabolic disorders, do not develop malignancy. The mechanisms of KLF10 in PDAC progression deserve further exploration. KLF10-depleted and KLF10-overexpressing PDAC cells were established to measure epithelial-mesenchymal transition (EMT), glycolysis, and migration ability. A murine model was established to evaluate the benefit of genetic or pharmacological manipulation in KLF10-depleted PDAC cells (PDACshKLF10). Correlations of KLF10 deficiency with rapid metastasis, elevated EMT, and glycolysis were demonstrated in resected PDAC tissues, in vitro assays, and murine models. We identified sirtuin 6 (SIRT6) as an essential mediator of KLF10 that modulates EMT and glucose homeostasis. Overexpressing SIRT6 reversed the migratory and glycolytic phenotypes of PDACshKLF10 cells. Linoleic acid, a polyunsaturated essential fatty acid, upregulated SIRT6 and prolonged the survival of mice injected with PDACshKLF10. Modulating HIF1α and NFκB revealed that EMT and glycolysis in PDAC cells were coordinately regulated upstream by KLF10/SIRT6 signaling. Our study demonstrated a novel KLF10/SIRT6 pathway that modulated EMT and glycolysis coordinately via NFκB and HIF1α. Activation of KLF10/SIRT6 signaling ameliorated the distant progression of PDAC.Clinical Trial Registration: ClinicalTrials.gov. identifier: NCT01666184.

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RETRACTED ARTICLE: Correlations between chromobox homolog 8 and key factors of epithelial–mesenchymal transition in hepatocellular carcinoma

Cancer Cell International ◽

10.1186/s12935-019-1063-z ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Xiaonian Zhu ◽

Wei Luo ◽

Chunhua Bei ◽

Juan Kong ◽

Shidong Zhang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Epithelial Mesenchymal Transition ◽

Migration Ability ◽

Mesenchymal Transition ◽

Invasion And Migration ◽

Knock Down ◽

Retracted Article ◽

Associated Proteins ◽

And Migration ◽

Hcc Cells

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, especially in China, with high metastasis and poor prognosis. Recently, as the core component of the polycomb repressive complexes 1 (PRC1), chromobox protein homolog 8 (CBX8) is considered as an oncogene and prognostic marker in HCC. Methods A tissue microarray of 166 paired HCC and adjacent non-tumor samples were collected to identify the relationship between CBX8 and epithelial mesenchymal transition (EMT) associated proteins by Spearman correlation analysis. Knock-down of CBX8 in HCC cells was conducted to detect the biologic functions of CBX8 in HCC metastasis. Results We found out that CBX8 was over-expressed in HCC and its expression was closely related to the metastasis of HCC patients. In addition, knock-down of CBX8 was found to inhibit the invasion and migration ability of HCC cells. Moreover, there was a significant relationship between expression of CBX8 and EMT associated proteins both in HCC cells and tumor tissues. Conclusions Our results indicate that CBX8 promotes metastasis of HCC by inducing EMT process.

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