Long non-coding RNA TUG1 knockdown hinders the tumorigenesis of multiple myeloma by regulating the microRNA-34a-5p/NOTCH1 signaling pathway
Multiple myeloma (MM) is a serious health issue in hematological malignancies. Long non-coding RNA taurine-upregulated gene 1 (TUG1) has been reported to be highly expressed in the plasma of MM patients. However, the functions of TUG1 in MM tumorigenesis along with related molecular basis are still...
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| Format: | Article |
| Language: | English |
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De Gruyter
2020-06-01
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| Series: | Open Life Sciences |
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| Online Access: | https://doi.org/10.1515/biol-2020-0025 |
| _version_ | 1797998128705568768 |
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| author | Zhang Yongtian Zhao Dandan Li Shumei Xiao Meng Zhou Hongjing Yang Shuige Hao Yunliang Dong Shasha |
| author_facet | Zhang Yongtian Zhao Dandan Li Shumei Xiao Meng Zhou Hongjing Yang Shuige Hao Yunliang Dong Shasha |
| author_sort | Zhang Yongtian |
| collection | DOAJ |
| description | Multiple myeloma (MM) is a serious health issue in hematological malignancies. Long non-coding RNA taurine-upregulated gene 1 (TUG1) has been reported to be highly expressed in the plasma of MM patients. However, the functions of TUG1 in MM tumorigenesis along with related molecular basis are still undefined. In this study, increased TUG1 and decreased microRNA-34a-5p (miR-34a-5p) levels in MM tissues and cells were measured by the real-time quantitative polymerase reaction assay. The expression of relative proteins was determined by the Western blot assay. TUG1 knockdown suppressed cell viability, induced cell cycle arrest and cell apoptosis in MM cells, as shown by Cell Counting Kit-8 and flow cytometry assays. Bioinformatics analysis, luciferase reporter assay, and RNA pull-down assay indicated that miR-34a-5p was a target of TUG1 and directly bound to notch receptor 1 (NOTCH1), and TUG1 regulated the NOTCH1 expression by targeting miR-34a-5p. The functions of miR-34a-5p were abrogated by TUG1 upregulation. Moreover, TUG1 loss impeded MM xenograft tumor growth in vivo by upregulating miR-34a-5p and downregulating NOTCH1. Furthermore, TUG1 depletion inhibited the expression of Hes-1, Survivin, and Bcl-2 protein in MM cells and xenograft tumors. TUG1 knockdown inhibited MM tumorigenesis by regulating the miR-34a-5p/NOTCH1 signaling pathway in vitro and in vivo, deepening our understanding of the TUG1 function in MM. |
| first_indexed | 2024-04-11T10:43:41Z |
| format | Article |
| id | doaj.art-af29bcbe393c44a79ff4ab6443bcb0fe |
| institution | Directory Open Access Journal |
| issn | 2391-5412 |
| language | English |
| last_indexed | 2024-04-11T10:43:41Z |
| publishDate | 2020-06-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Open Life Sciences |
| spelling | doaj.art-af29bcbe393c44a79ff4ab6443bcb0fe2022-12-22T04:29:08ZengDe GruyterOpen Life Sciences2391-54122020-06-0115128429510.1515/biol-2020-0025biol-2020-0025Long non-coding RNA TUG1 knockdown hinders the tumorigenesis of multiple myeloma by regulating the microRNA-34a-5p/NOTCH1 signaling pathwayZhang Yongtian0Zhao Dandan1Li Shumei2Xiao Meng3Zhou Hongjing4Yang Shuige5Hao Yunliang6Dong Shasha7Department of Hematology, Ji’ning No. 1 People’s Hospital, Ji’ning, Shandong, ChinaDepartment of Hematology, Ji’ning No. 1 People’s Hospital, Ji’ning, Shandong, ChinaDepartment of Hematology, Ji’ning No. 1 People’s Hospital, Ji’ning, Shandong, ChinaDepartment of Hematology, Ji’ning No. 1 People’s Hospital, Ji’ning, Shandong, ChinaDepartment of Hematology, Ji’ning No. 1 People’s Hospital, Ji’ning, Shandong, ChinaDepartment of Hematology, Ji’ning No. 1 People’s Hospital, Ji’ning, Shandong, ChinaDepartment of Hematology, Ji’ning No. 1 People’s Hospital, Ji’ning, Shandong, ChinaDepartment of Hematology, Ji’ning No. 1 People’s Hospital, Ji’ning, Shandong, ChinaMultiple myeloma (MM) is a serious health issue in hematological malignancies. Long non-coding RNA taurine-upregulated gene 1 (TUG1) has been reported to be highly expressed in the plasma of MM patients. However, the functions of TUG1 in MM tumorigenesis along with related molecular basis are still undefined. In this study, increased TUG1 and decreased microRNA-34a-5p (miR-34a-5p) levels in MM tissues and cells were measured by the real-time quantitative polymerase reaction assay. The expression of relative proteins was determined by the Western blot assay. TUG1 knockdown suppressed cell viability, induced cell cycle arrest and cell apoptosis in MM cells, as shown by Cell Counting Kit-8 and flow cytometry assays. Bioinformatics analysis, luciferase reporter assay, and RNA pull-down assay indicated that miR-34a-5p was a target of TUG1 and directly bound to notch receptor 1 (NOTCH1), and TUG1 regulated the NOTCH1 expression by targeting miR-34a-5p. The functions of miR-34a-5p were abrogated by TUG1 upregulation. Moreover, TUG1 loss impeded MM xenograft tumor growth in vivo by upregulating miR-34a-5p and downregulating NOTCH1. Furthermore, TUG1 depletion inhibited the expression of Hes-1, Survivin, and Bcl-2 protein in MM cells and xenograft tumors. TUG1 knockdown inhibited MM tumorigenesis by regulating the miR-34a-5p/NOTCH1 signaling pathway in vitro and in vivo, deepening our understanding of the TUG1 function in MM.https://doi.org/10.1515/biol-2020-0025long non-coding rnatug1microrna-34a-5pnotch1multiple myeloma |
| spellingShingle | Zhang Yongtian Zhao Dandan Li Shumei Xiao Meng Zhou Hongjing Yang Shuige Hao Yunliang Dong Shasha Long non-coding RNA TUG1 knockdown hinders the tumorigenesis of multiple myeloma by regulating the microRNA-34a-5p/NOTCH1 signaling pathway Open Life Sciences long non-coding rna tug1 microrna-34a-5p notch1 multiple myeloma |
| title | Long non-coding RNA TUG1 knockdown hinders the tumorigenesis of multiple myeloma by regulating the microRNA-34a-5p/NOTCH1 signaling pathway |
| title_full | Long non-coding RNA TUG1 knockdown hinders the tumorigenesis of multiple myeloma by regulating the microRNA-34a-5p/NOTCH1 signaling pathway |
| title_fullStr | Long non-coding RNA TUG1 knockdown hinders the tumorigenesis of multiple myeloma by regulating the microRNA-34a-5p/NOTCH1 signaling pathway |
| title_full_unstemmed | Long non-coding RNA TUG1 knockdown hinders the tumorigenesis of multiple myeloma by regulating the microRNA-34a-5p/NOTCH1 signaling pathway |
| title_short | Long non-coding RNA TUG1 knockdown hinders the tumorigenesis of multiple myeloma by regulating the microRNA-34a-5p/NOTCH1 signaling pathway |
| title_sort | long non coding rna tug1 knockdown hinders the tumorigenesis of multiple myeloma by regulating the microrna 34a 5p notch1 signaling pathway |
| topic | long non-coding rna tug1 microrna-34a-5p notch1 multiple myeloma |
| url | https://doi.org/10.1515/biol-2020-0025 |
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