scholarly journals Differentially expressed microRNAs in bone marrow mesenchymal stem cell-derived microvesicles in young and older rats and their effect on tumor growth factor-β1-mediated epithelial-mesenchymal transition in HK2 cells

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Yan Wang ◽  
Bo Fu ◽  
Xuefeng Sun ◽  
Diangeng Li ◽  
Qi Huang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Growth Factor ◽  
Mesenchymal Stem Cell ◽  
Tumor Growth ◽  
Epithelial Mesenchymal Transition ◽  
Differentially Expressed ◽  
Mesenchymal Transition ◽  
Tumor Growth Factor ◽  
Hk2 Cells

scholarly journals Human umbilical cord mesenchymal stem cell-derived exosomal miR-27b attenuates subretinal fibrosis via suppressing epithelial–mesenchymal transition by targeting HOXC6

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dongli Li ◽  
Junxiu Zhang ◽  
Zijia Liu ◽  
Yuanyuan Gong ◽  
Zhi Zheng
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Umbilical Cord ◽  
Mechanism Of Action ◽  
Epithelial Mesenchymal Transition ◽  
Human Umbilical Cord ◽  
Mesenchymal Transition ◽  
Rpe Cells ◽  
Subretinal Fibrosis

Abstract Background and aim Subretinal fibrosis resulting from neovascular age-related macular degeneration (nAMD) is one of the major causes of serious and irreversible vision loss worldwide, and no definite and effective treatment exists currently. Retinal pigmented epithelium (RPE) cells are crucial in maintaining the visual function of normal eyes and its epithelial–mesenchymal transition (EMT) is associated with the pathogenesis of subretinal fibrosis. Stem cell-derived exosomes have been reported to play a crucial role in tissue fibrosis by transferring their molecular contents. This study aimed to explore the effects of human umbilical cord-derived mesenchymal stem cell exosomes (hucMSC-Exo) on subretinal fibrosis in vivo and in vitro and to investigate the anti-fibrotic mechanism of action of hucMSC-Exo. Methods In this study, human umbilical cord-derived mesenchymal stem cells (hucMSCs) were successfully cultured and identified, and exosomes were isolated from the supernatant by ultracentrifugation. A laser-induced choroidal neovascularization (CNV) and subretinal fibrosis model indicated that the intravitreal administration of hucMSC-Exo effectively alleviated subretinal fibrosis in vivo. Furthermore, hucMSC-Exo could efficaciously suppress the migration of retinal pigmented epithelial (RPE) cells and promote the mesenchymal–epithelial transition by delivering miR-27b-3p. The latent binding of miR-27b-3p to homeobox protein Hox-C6 (HOXC6) was analyzed by bioinformatics prediction and luciferase reporter assays. Results This study showed that the intravitreal injection of hucMSC-Exo effectively ameliorated laser-induced CNV and subretinal fibrosis via the suppression of epithelial–mesenchymal transition (EMT) process. In addition, hucMSC-Exo containing miR-27b repressed the EMT process in RPE cells induced by transforming growth factor-beta2 (TGF-β2) via inhibiting HOXC6 expression. Conclusions The present study showed that HucMSC-derived exosomal miR-27b could reverse the process of EMT induced by TGF-β2 via inhibiting HOXC6, indicating that the exosomal miR-27b/HOXC6 axis might play a vital role in ameliorating subretinal fibrosis. The present study proposed a promising therapeutic agent for treating ocular fibrotic diseases and provided insights into the mechanism of action of hucMSC-Exo on subretinal fibrosis.

scholarly journals RUNX1 suppresses breast cancer stemness and tumor growth

2018 ◽  
Author(s):  
Deli Hong ◽  
Andrew J. Fritz ◽  
Kristiaan H. Finstad ◽  
Mark P. Fitzgerald ◽  
Adam L. Viens ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Tumor Suppressor ◽  
Cancer Stem Cell ◽  
Tumor Growth ◽  
Epithelial Mesenchymal Transition ◽  
Ectopic Expression ◽  
Cell Activity ◽  
Mesenchymal Transition

SummaryRecent studies have revealed that mutations in the transcription factor Runx1 are prevalent in breast tumors. Yet, how loss of Runx1 contributes to breast cancer (BCa) remains unresolved. We demonstrate for the first time that Runx1 represses the breast cancer stem cell (BCSC) phenotype and consequently, functions as a tumor suppressor in breast cancer. Runx1 ectopic expression in MCF10AT1 and MCF10CA1a BCa cells reduces (60%) migration, invasion and in vivo tumor growth in mouse mammary fat pad (P<0.05). Runx1 is decreased in BCSCs, and overexpression of Runx1 suppresses tumorsphere formation and reduces the BCSC population. Furthermore, Runx1 inhibits Zeb1 expression, while Runx1 depletion activates Zeb1 and the epithelial-mesenchymal transition. Mechanistically Runx1 functions as a tumor suppressor in breast cancer through repression of cancer stem cell activity. This key regulation of BCSCs by Runx1 may be shared in other epithelial carcinomas, highlighting the importance of Runx1 in solid tumors.

scholarly journals Bone Marrow-Derived Myofibroblasts Contribute to the Mesenchymal Stem Cell Niche and Promote Tumor Growth

Cancer Cell ◽  
2011 ◽  
Vol 19 (2) ◽  
pp. 257-272 ◽  
Author(s):  
Michael Quante ◽  
Shui Ping Tu ◽  
Hiroyuki Tomita ◽  
Tamas Gonda ◽  
Sophie S.W. Wang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Tumor Growth ◽  
Stem Cell Niche ◽  
Promote Tumor Growth ◽  
Cell Niche

Involvement of miRNAs in the formation and maintenance of self-renewing kidney cancer spheres with stem cell properties.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 463-463
Author(s):  
Zsuzsanna Lichner ◽  
Carol Saleh ◽  
Venkateshwaran Subramaniam ◽  
Gerard Prud'homme ◽  
George M. Yousef
Keyword(s):  
Stem Cell ◽  
Mirna Expression ◽  
Epithelial Mesenchymal Transition ◽  
Target Prediction ◽  
Tumor Model ◽  
Defined Medium ◽  
Differentially Expressed ◽  
Mesenchymal Transition ◽  
Immunodeficient Mice ◽  
Qrt Pcr

463 Background: Cancer cells may acquire stem cell (CSC) properties by activated TGFβ-epithelial-mesenchymal transition (EMT) axis resulting in formation of cancer stem cells. miRNAs are involved in CSC formation in solid tumors, but their role has not been investigated in renal cell carcinoma (RCC). Methods: RCC spheres were generated and propagated in serum-free defined medium (SFDM). mRNA expression was assessed by qRT-PCR. miRNA expression was screened on a qRT-PCR based panel. Tumorigenicity was assessed by subcutaneous injection of RCC sphere or parental cells into immunodeficient mice in different dilutions. TargetScan and miRPath was used for target prediction and clustering. Results: We isolated self-renewing cancer spheres from ACHN and CAKI-1 RCC cell lines in the stem cell supporting media, SFDM. Spheres were highly clonogenic and tumorigenic in xenograft tumor model and expressed high levels of stem cell-related markers and mesenchymal markers. These spheres were enriched in the mesenchymal marker CD44 and the kidney progenitor maker CD24 indicating that EMT contributed to their formation or maintenance. We compared miRNA expression between the spheres and the parental cells and identified differentially expressed miRNAs. Functional clustering of their predicted targets indicates that TGFβ signaling is a potential regulator of CSC self-renewal and is regulated by the candidate miRNAs. Further, we show that transfection of ACHN and CAKI-1 cells with the miR-17 inhibitor resulted in rapid and highly efficient formation of cancer spheres that were indistinguishable from the spheres formed in SFDM. These spheres were stable and could be propagated indefinitely. Histologic examination and immunohistochemistry of the sphere-derived xenografts confirmed the presence of clear cell RCC with large areas of sarcomatoid dedifferentiation. Finally, we prove that the TGFβ receptor II, and the co-Smad Smad4 are possible direct targets of miR-17. Conclusions: The TGFβ-EMT axis likely contributes to the self-renewing potential of RCC spheres. miRNAs are differentially expressed in RCC spheres and miR-17 inhibition transformed ccRCC cells to highly tumorigenic RCC spheres.

Sign in / Sign up

Export Citation Format

Share Document