scholarly journals ZEB1 Mediates Bone Marrow Mesenchymal Stem Cell Osteogenic Differentiation Partly via Wnt/β-Catenin Signaling

2021 ◽  
Vol 8 ◽  
Author(s):  
Cuidi Xu ◽  
Hongli Shi ◽  
Xin Jiang ◽  
Yongqian Fan ◽  
Donghui Huang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Transcription Factor ◽  
Osteogenic Differentiation ◽  
Zinc Finger ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Marrow Mesenchymal Stem Cells ◽  
Zeb1 Expression

Zinc finger E-box-binding homebox 1 (ZEB1) is a zinc-finger transcription factor best known for its role in promoting the epithelial-mesenchymal transition, which is also related to osteogenesis. Here, ZEB1 was investigated for its role in the commitment of bone marrow mesenchymal stem cells (BMSCs) to osteoblasts. In vitro, ZEB1 expression decreased following osteogenic differentiation. Furthermore, silencing of ZEB1 in BMSCs promoted osteogenic activity and mineralization. The increase in osteogenic differentiation induced by si-ZEB1 could be partly rescued by the inhibition of Wnt/β-catenin (si-β-catenin). In vivo, knockdown of ZEB1 in BMSCs inhibited the rapid bone loss of ovariectomized (OVX) mice. ZEB1 expression has also been negatively associated with bone mass and bone formation in postmenopausal women. In conclusion, ZEB1 is an essential transcription factor in BMSC differentiation and may serve as a potential anabolic strategy for treating and preventing postmenopausal osteoporosis (PMOP).

scholarly journals Transcription factor Mohawk controls tenogenic differentiation of bone marrow mesenchymal stem cells in vitro and in vivo

2014 ◽  
Vol 33 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Koji Otabe ◽  
Hiroyuki Nakahara ◽  
Akihiko Hasegawa ◽  
Tetsuya Matsukawa ◽  
Fumiaki Ayabe ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Transcription Factor ◽  
Tenogenic Differentiation ◽  
Marrow Mesenchymal Stem Cells

scholarly journals Bone morphogenetic protein-7 prevented epithelial-mesenchymal transition in RLE-6TN cells

2016 ◽  
Vol 5 (3) ◽  
pp. 931-937 ◽  
Author(s):  
Yan Wang ◽  
Di Liang ◽  
Zhonghui Zhu ◽  
Xiaoli Li ◽  
Guoliang An ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Bone Morphogenetic Protein ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Epithelial Mesenchymal Transition ◽  
Bone Morphogenetic Protein 7 ◽  
Mesenchymal Transition ◽  
Morphogenetic Protein

Silica induced EMT and decreased the expression of BMP-7 in vivo and in vitro, while exogenous BMP-7 promoted MET and inhibited silica-induced EMT associated with inhibition of the p38 MAPK/transcription factor (TF) signaling pathway in RLE-6TN cells.

miR-653 Induces Bone Marrow Mesenchymal Stem Cells Proliferation via Activating Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma

2022 ◽  
Vol 12 (2) ◽  
pp. 381-385
Author(s):  
Cui Qin ◽  
Yibo Xiang ◽  
Sheng Li ◽  
Shu Huang ◽  
Wenjun Chen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Transcription Factor ◽  
Epithelial Mesenchymal Transition ◽  
Biological Mechanism ◽  
Rt Pcr ◽  
Mesenchymal Transition ◽  
Qrt Pcr ◽  
Marrow Mesenchymal Stem Cells

This study intends to assess miR-653’s expression in MSCs and OSCC and discuss molecular biological mechanism of changes of EMT in MSCs through activating miR-653 in OSCC. miR-653 expression in MSCs and OSCC was detected. si-miR-653 was transfected into MSCs followed by analysis of cell proliferation by CCK-8 and clone formation assay, cell apoptosis and cycle by FCM, and the changes of transcription factor as ZEB1 and Snail by qRT-PCR. miR-653 expression in OSCC cell was up-regulated significantly from the result of q-RT-PCR detection. The proliferation of MSCs induced by miR-653 was restrained and apoptotic rate was increased after treatment with si-miR-653 along with stagnated cycle of G1/G0 staging cell. The expression of transcription factor of EMT type as ZEB1 and Snail was elevated significantly after intervention using si-miR-653. In conclusion, the proliferation of OSCC could be induced by MSCs through activation with miR-653 which might be through regulation of EMT process.

scholarly journals Long non-coding RNA MIR22HG promotes osteogenic differentiation of bone marrow mesenchymal stem cells via PTEN/ AKT pathway

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Chanyuan Jin ◽  
Lingfei Jia ◽  
Zhihui Tang ◽  
Yunfei Zheng
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Mineral Density ◽  
Tensin Homolog ◽  
Human Bmscs ◽  
Marrow Mesenchymal Stem Cells

Abstract Osteoporosis is a prevalent metabolic bone disease characterized by low bone mineral density and degenerative disorders of bone tissues. Previous studies showed the abnormal osteogenic differentiation of endogenous bone marrow mesenchymal stem cells (BMSCs) contributes to the development of osteoporosis. However, the underlying mechanisms by which BMSCs undergo osteogenic differentiation remain largely unexplored. Recently, long non-coding RNAs have been discovered to play important roles in regulating BMSC osteogenesis. In this study, we first showed MIR22HG, which has been demonstrated to be involved in the progression of several cancer types, played an important role in regulating BMSC osteogenesis. We found the expression of MIR22HG was significantly decreased in mouse BMSCs from the osteoporotic mice and it was upregulated during the osteogenic differentiation of human BMSCs. Overexpression of MIR22HG in human BMSCs enhanced osteogenic differentiation, whereas MIR22HG knockdown inhibited osteogenic differentiation both in vitro and in vivo. Mechanistically, MIR22HG promoted osteogenic differentiation by downregulating phosphatase and tensin homolog (PTEN) and therefore activating AKT signaling. Moreover, we found MIR22HG overexpression promoted osteoclastogenesis of RAW264.7 cells, which indicated that MIR22HG played a significant role in bone metabolism and could be a therapeutic target for osteoporosis and other bone-related diseases.

scholarly journals LINC00152 upregulates ZEB1 expression and enhances epithelial-mesenchymal transition and oxaliplatin resistance in esophageal cancer by interacting with EZH2

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Shuyao Zhang ◽  
Wei Liao ◽  
Qinshui Wu ◽  
Xiaoshan Huang ◽  
Zhen Pan ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Expression Patterns ◽  
Special Focus ◽  
Loss Of Function ◽  
Mesenchymal Transition ◽  
Ec Cells ◽  
Zeb1 Expression

Abstract Background Expression of the long non-coding mRNA LINC00152 has been reported to correlate with cancer cell resistance to oxaliplatin (L-OHP). However, little is known regarding the molecular mechanism of LINC00152 in esophageal cancer (EC). Hence, we intended to characterize the role of LINC00152 in EC, with a special focus on epithelial-mesenchymal transition (EMT) and L-OHP resistance. Methods We collected EC tissues and identified EC cell lines with higher L-OHP resistance, and then characterized expression patterns of LINC00152, Zeste Homologue 2 (EZH2), Zinc finger e-box binding homeobox (ZEB1) and EMT-related genes using RT-qPCR and Western blot analysis. Furthermore, their functional significance was identified by gain and loss-of-function experiments. The relationship among LINC00152, EZH2 and ZEB1 was examined using RIP, RNA pull-down and ChIP assays. Additionally, resistance of EC cells to L-OHP was reflected by CCK-8 assay to detect cell viability. Animal experiments were also conducted to detect the effects of the LINC00152/EZH2/ZEB1 on EMT and L-OHP resistance. Results LINC00152, EZH2 and ZEB1 were highly expressed in EC tissues and Kyse−150/TE-1 cells. As revealed by assays in vitro and in vivo, LINC00152 positively regulated ZEB1 expression through interaction with EZH2 to enhance EMT and L-OHP resistance in EC cells. In contrast, silencing of LINC00152 contributed to attenuated EMT and drug resistance of EC cells to L-OHP. Conclusions Our study demonstrates that LINC00152/EZH2/ZEB1 axis can regulate EMT and resistance of EC cells to L-OHP, thus presenting a potential therapeutic target for EC treatment.

scholarly journals MicroRNA-15b shuttled by bone marrow mesenchymal stem cell-derived extracellular vesicles binds to WWP1 and promotes osteogenic differentiation

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Yanhong Li ◽  
Jing Wang ◽  
Yanchao Ma ◽  
Wenjia Du ◽  
Haijun Feng ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Loss ◽  
Osteogenic Differentiation ◽  
Extracellular Vesicles ◽  
Ovariectomized Rats ◽  
Luciferase Reporter ◽  
Human Bmscs ◽  
Marrow Mesenchymal Stem Cells

Abstract Background Osteogenic differentiation is an essential process for bone regeneration involving bone marrow mesenchymal stem cells (BMSCs). BMSC-secreted extracellular vesicles (EVs) enriched with microRNAs (miRs) have vital roles to play in mediating osteogenic differentiation. Therefore, this study aimed to explore the effect of BMSC-derived EVs loaded with miR-15b on osteogenic differentiation. Methods Human BMSCs (hBMSCs) were cultured and treated with plasmids overexpressing or knocking down KLF2, WWP1, and miR-15b to define the role of derived EVs in osteogenic differentiation in vitro. The expression of osteogenic differentiation-related marker was measured by Western blot analysis. The interaction among miR-15b, WWP1, and ubiquitination of KLF2 was investigated by dual-luciferase reporter, immunoprecipitation, and GST pull-down assays. Moreover, EVs from hBMSCs transfected with miR-15b inhibitor (EV-miR-15b inhibitor) were injected into ovariectomized rats to verify the effect of miR-15b on bone loss in vivo. Results WWP1 was downregulated, and KLF2 was upregulated during osteogenic differentiation. After co-culture with EVs, miR-15b expression was elevated and WWP1 expression was reduced in hBMSCs. Upregulation of miR-15b or KLF2 or downregulation of WWP1 or NF-κB increased ALP activity and cell mineralization, as well as osteogenic differentiation-related marker expression in hBMSCs. Mechanistically, miR-15b targeted and inhibited WWP1, thus attenuating KLF2 degradation and inhibiting NF-κB activity. Co-culture of EVs increased the bone volume and trabecular number, but decreased bone loss in ovariectomized rats, which could be reversed after treatment with EV-miR-15b inhibitor. Conclusion Collectively, BMSC-derived EVs loaded with miR-15b promoted osteogenic differentiation by impairing WWP1-mediated KLF2 ubiquitination and inactivating the NF-κB signaling pathway. Graphical abstract

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 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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