Identification of miRNA signature associated with BMP2 and chemosensitivity of TMZ in glioblastoma stem-like cells
Glioblastoma multiform (GBM) is the most lethal intracranial tumor in adults. Glioblastoma stem-like cells (GSCs) are responsible for tumorigenesis and chemotherapy resistance. BMPs are known to increase temozolomide (TMZ) response in GSCs, however, the intracellular molecular mechanism remains larg...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2020-09-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304219300674 |
| _version_ | 1827267391715803136 |
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| author | Xiaoyu Guo Ziguo Luo Tong Xia Lanxiang Wu Yanshu Shi Ying Li |
| author_facet | Xiaoyu Guo Ziguo Luo Tong Xia Lanxiang Wu Yanshu Shi Ying Li |
| author_sort | Xiaoyu Guo |
| collection | DOAJ |
| description | Glioblastoma multiform (GBM) is the most lethal intracranial tumor in adults. Glioblastoma stem-like cells (GSCs) are responsible for tumorigenesis and chemotherapy resistance. BMPs are known to increase temozolomide (TMZ) response in GSCs, however, the intracellular molecular mechanism remains largely unknown. In this study, we built a GSC cell model called U87S, and performed RNA sequencing to identify differentially expressed (DE) miRNA profiles in U87S cells treated with BMP2, TMZ or combined BMP2 and TMZ respectively. Bioinformatics analysis revealed that most DE miRNAs were involved in the cancer pathways, suggesting their crucial roles in gliomagenesis. Eight miRNAs from RNA-seq were validated. Four out of these miRNAs (has-miR-199a-3p, hsa-miR-374b-5p, hsa-miR-320d, and hsa-miR-339-5p) were found significantly up-regulated in GBM tumor tissues. One of them, hsa-miR-199a-3p, was significantly correlated with the survival of GBM patients, and differentially expressed in U87S cells. Expression of hsa-miR-199a-3p was up-regulated by BMP. Overexpression of hsa-miR-199a-3p in U87S cells inhibited cell viability and enhanced the cytotoxicity of TMZ. And activation of BMP boosted the effect of hsa-miR-199a-3p on cell viability and TMZ-mediated cytotoxicity. Besides, expressions of five predicted targets of hsa-miR-199a-3p were evaluated. Four of them were differentially expressed in GBM tumors. And one of them, SLC22A18, was associated with the survival of GBM patients. In the end, a hsa-miR-199a-3p-mediated ceRNA network was constructed for the convenience of future study. Together, our data provided DE miRNA expression profiles associated with BMP2 and TMZ in GSCs, which might lead to finding out miRNA-based target therapies that specially target GSCs. |
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| institution | Directory Open Access Journal |
| issn | 2352-3042 |
| language | English |
| last_indexed | 2025-03-22T04:33:00Z |
| publishDate | 2020-09-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Genes and Diseases |
| spelling | doaj.art-1898039a139e4b548bc11142edf0dc9a2024-04-28T02:15:44ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422020-09-0173424439Identification of miRNA signature associated with BMP2 and chemosensitivity of TMZ in glioblastoma stem-like cellsXiaoyu Guo0Ziguo Luo1Tong Xia2Lanxiang Wu3Yanshu Shi4Ying Li5Life Science Institute, Chongqing Medical University, Chongqing, ChinaLife Science Institute, Chongqing Medical University, Chongqing, ChinaLife Science Institute, Chongqing Medical University, Chongqing, ChinaLife Science Institute, Chongqing Medical University, Chongqing, ChinaDepartment of Radiology, Southwest Hospital, Third Military Medical University, Chongqing, ChinaLife Science Institute, Chongqing Medical University, Chongqing, China; Corresponding author. Life Science Institute, Chongqing Medical University, 1 Xueyuan Road, District Yuzhong, Chongqing, 400016, China.Glioblastoma multiform (GBM) is the most lethal intracranial tumor in adults. Glioblastoma stem-like cells (GSCs) are responsible for tumorigenesis and chemotherapy resistance. BMPs are known to increase temozolomide (TMZ) response in GSCs, however, the intracellular molecular mechanism remains largely unknown. In this study, we built a GSC cell model called U87S, and performed RNA sequencing to identify differentially expressed (DE) miRNA profiles in U87S cells treated with BMP2, TMZ or combined BMP2 and TMZ respectively. Bioinformatics analysis revealed that most DE miRNAs were involved in the cancer pathways, suggesting their crucial roles in gliomagenesis. Eight miRNAs from RNA-seq were validated. Four out of these miRNAs (has-miR-199a-3p, hsa-miR-374b-5p, hsa-miR-320d, and hsa-miR-339-5p) were found significantly up-regulated in GBM tumor tissues. One of them, hsa-miR-199a-3p, was significantly correlated with the survival of GBM patients, and differentially expressed in U87S cells. Expression of hsa-miR-199a-3p was up-regulated by BMP. Overexpression of hsa-miR-199a-3p in U87S cells inhibited cell viability and enhanced the cytotoxicity of TMZ. And activation of BMP boosted the effect of hsa-miR-199a-3p on cell viability and TMZ-mediated cytotoxicity. Besides, expressions of five predicted targets of hsa-miR-199a-3p were evaluated. Four of them were differentially expressed in GBM tumors. And one of them, SLC22A18, was associated with the survival of GBM patients. In the end, a hsa-miR-199a-3p-mediated ceRNA network was constructed for the convenience of future study. Together, our data provided DE miRNA expression profiles associated with BMP2 and TMZ in GSCs, which might lead to finding out miRNA-based target therapies that specially target GSCs.http://www.sciencedirect.com/science/article/pii/S2352304219300674BMP2Cancer stem cellCeRNAGliobalstomaRNA-seqTMZ |
| spellingShingle | Xiaoyu Guo Ziguo Luo Tong Xia Lanxiang Wu Yanshu Shi Ying Li Identification of miRNA signature associated with BMP2 and chemosensitivity of TMZ in glioblastoma stem-like cells Genes and Diseases BMP2 Cancer stem cell CeRNA Gliobalstoma RNA-seq TMZ |
| title | Identification of miRNA signature associated with BMP2 and chemosensitivity of TMZ in glioblastoma stem-like cells |
| title_full | Identification of miRNA signature associated with BMP2 and chemosensitivity of TMZ in glioblastoma stem-like cells |
| title_fullStr | Identification of miRNA signature associated with BMP2 and chemosensitivity of TMZ in glioblastoma stem-like cells |
| title_full_unstemmed | Identification of miRNA signature associated with BMP2 and chemosensitivity of TMZ in glioblastoma stem-like cells |
| title_short | Identification of miRNA signature associated with BMP2 and chemosensitivity of TMZ in glioblastoma stem-like cells |
| title_sort | identification of mirna signature associated with bmp2 and chemosensitivity of tmz in glioblastoma stem like cells |
| topic | BMP2 Cancer stem cell CeRNA Gliobalstoma RNA-seq TMZ |
| url | http://www.sciencedirect.com/science/article/pii/S2352304219300674 |
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