Title |
Reciprocal activation between STAT3 and miR-181b regulates the proliferation of esophageal cancer stem-like cells via the CYLD pathway
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Published in |
Molecular Cancer, May 2016
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DOI | 10.1186/s12943-016-0521-7 |
Pubmed ID | |
Authors |
Dan-dan Xu, Peng-jun Zhou, Ying Wang, Li Zhang, Wu-yu Fu, Bi-bo Ruan, Hai-peng Xu, Chao-zhi Hu, Lu Tian, Jin-hong Qin, Sheng Wang, Xiao Wang, Yi-cheng Li, Qiu-ying Liu, Zhe Ren, Rong Zhang, Yi-fei Wang |
Abstract |
Recent studies have suggested that cancer cells contain subpopulations that can initiate tumor growth, self-renew, and maintain tumor cell growth. However, for esophageal cancer cells, the relationship between STAT3, microRNAs and cancer stem cells remains unclear. Serum-free culture was used to enrich esophageal cancer stem-like cells (ECSLC). Flow cytometry determined the proportion of ECSLC. qPCR were performed to examine expression level of stemness factors, mesenchymal markers, ATP-binding cassette (ABC) transporters, STAT3, miR-181b, CYLD. Western blot were performed to analyze the expression of STAT3, p-STAT3 and CYLD (cylindromatosis). BALB/c mice xenograft studies were conducted to evaluate the tumorigenicity of enriched ECSLC. Sphere formation assay and colony formation assays were employed to analyze the relationship between STAT3 and miR-181b. Luciferase assays were used to evaluate activity which CYLD is a target of miR-181b. Sphere formation cells (SFCs) with properties of ECSLC were enriched. Enriched SFCs in serum-free suspension culture exhibited cancer stem-like cell properties and increased single-positive CD44 + CD24-, stemness factor, mesenchymal marker expression ABC transporters and tumorigenicity in vivo compared with the parental cells. Additionally, we found that reciprocal activation between STAT3 and miR-181b regulated SFCs proliferation. Moreover, STAT3 directly activated miR-181b transcription in SFCs and miR-181b then potentiated p-STAT3 activity. Luciferase assays indicated that CYLD was a direct and functional target of miR-181b. The mutual regulation between STAT3 and miR-181b in SFCs was required for proliferation and apoptosis resistance. STAT3 and miR-181b control each other's expression in a positive feedback loop that regulates SFCs via CYLD pathway. These findings maybe is helpful for targeting ECSLC and providing approach for esophageal cancer treatments. |
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Demographic breakdown
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Members of the public | 2 | 67% |
Science communicators (journalists, bloggers, editors) | 1 | 33% |
Mendeley readers
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Unknown | 20 | 100% |
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Other | 2 | 10% |
Researcher | 2 | 10% |
Professor > Associate Professor | 2 | 10% |
Student > Doctoral Student | 1 | 5% |
Student > Master | 1 | 5% |
Other | 3 | 15% |
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Medicine and Dentistry | 2 | 10% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 5% |
Unknown | 9 | 45% |