Deletion of miR-15a inhibited glioma development via targeting Smad7 and inhibiting EMT pathway
| Autor: | Gang Li, Shien An, Yabin Li, Xin Li, Zhisheng Ji, Jianzhou Gao, Jixiang Liu, Xiaopeng Gao, Zhihuang Zhao, Hongyan Liu, Yanfeng Guo, Lekun Pan, Yonggang Han |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Aging Epithelial-Mesenchymal Transition Mice Nude medicine.disease_cause Smad7 Protein Mice Western blot In vivo Glioma Cell Line Tumor microRNA medicine Gene silencing Animals Humans Luciferase Gene Silencing medicine.diagnostic_test integumentary system miR-15a Smad7 Chemistry EMT Cell Biology medicine.disease MicroRNAs tumorigenesis Cell culture Cancer research Carcinogenesis Research Paper |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | In the present study, we found the expression of miR-15a-5p (miR-15a) was increased in glioma tissues, and we further explore the underlying mechanism of miR-15a in glioma progression. Microarray analysis used to identify the differentially expressed microRNAs (miRNAs) in glioma tissues. The expression of miR-15a in glioma tissues and cell lines was tested by qRT-PCR. Luciferase assay was used to determine the binding between miR-15a and Smad7. Wound healing and transwell assay were used to examine the role of miR-15a/Smad7 in SHG139 cells. Western blot was used to detect the protein level of Smad7 and epithelial-mesenchymal transition (EMT) markers. A tumor formation model in nude mice was established to measure the role of miR-15a in vivo. MiR-15a was significantly increased in glioma tissues and cells, which indicated a poor prognosis of glioma patients. MiR-15a mimics induced miR-15a level in SHG139 cells, and promoted the malignancy of SHG139 cells, while miR-15a inhibitor showed the opposite effects. Luciferase assay indicated that Smad7 was the direct target of miR-15a, and Smad7 was down-regulated in glioma tissues. Functional experiments revealed that miR-15a inhibitor inhibited the EMT pathway and the migration and invasion of glioma cells, but the silencing of Smad7 reversed the effects of miR-15a inhibitor in EMT pathway and glioma progression. Finally, we performed animal experiments to verify the role of miR-15a in vivo. Present study showed that deletion of miR-15a inhibited the activation of EMT signaling via targeting Smad7, thus suppressed the tumorigenesis and tumor growth of glioma. |
| Databáze: | OpenAIRE |
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