LncRNA XIST from the bone marrow mesenchymal stem cell derived exosome promotes osteosarcoma growth and metastasis through miR-655/ACLY signal
Abstract Background Long non-coding RNA X-inactive specific transcript (XIST) regulates the progression of a variety of tumors, including osteosarcoma. Bone marrow mesenchymal stem cells (BMSCs) can be recruited into osteosarcoma tissue and affect the progression by secreting exosomes. However, whet...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-10-01
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| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12935-022-02746-0 |
| _version_ | 1811257189021515776 |
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| author | Guanghui Zhu Yu Xia Ziyue Zhao Aoyu Li Hui Li Tao Xiao |
| author_facet | Guanghui Zhu Yu Xia Ziyue Zhao Aoyu Li Hui Li Tao Xiao |
| author_sort | Guanghui Zhu |
| collection | DOAJ |
| description | Abstract Background Long non-coding RNA X-inactive specific transcript (XIST) regulates the progression of a variety of tumors, including osteosarcoma. Bone marrow mesenchymal stem cells (BMSCs) can be recruited into osteosarcoma tissue and affect the progression by secreting exosomes. However, whether BMSCs derived exosomes transmit XIST to regulate the growth and metastasis of osteosarcoma and the related mechanism are still unclear. Method In this study, BMSCs derived exosomes were used to treat human osteosarcoma cells MG63 and 143B, and the level of XIST in BMSCs was intervened by siRNA. CCK-8, EdU, transwell assays were used to analyze the changes of cell proliferation, migration and invasion. Bioinformatics analysis, RNA pulldown and dual-luciferase reporter gene assays validated the targeted relationship of XIST with miR-655 and the interaction between miR-655 and ACLY 3’-UTR. 143B/LUC cell line was used to establish an animal model of in situ osteosarcoma to verify the found effects of XIST on osteosarcoma. Oil Red O staining, Western blot and so on were used to detect the changes of lipid deposition and protein expression. Results It was found that BMSCs derived exosomes promoted the proliferation, migration and invasion of osteosarcoma cells, and the down-regulation of XIST inhibited this effect. miR-655 mediated the role of BMSCs derived exosomal XIST in promoting the progression of osteosarcoma and down-regulation of miR-655 could reverse the effects of inhibiting XIST on the proliferation, migration and invasion of osteosarcoma cells. Meanwhile, animal level results confirmed that BMSCs derived exosomal XIST could promote osteosarcoma growth and lung metastasis by combining with miR-655. In-depth mechanism study showed that BMSCs derived exosomal XIST combined with miR-655 to increase the protein level of ACLY, which led to lipid deposition and activate β-catenin signal to promote the proliferation, migration and invasion of osteosarcoma cells. Conclusion This study showed that BMSCs derived exosomal XIST could enter osteosarcoma cells, bind and down-regulates the level of miR-655, resulting in an increase in the level of ACLY, thus increasing the lipid deposition and the activity of β-catenin signal to promote the growth and metastasis of osteosarcoma. |
| first_indexed | 2024-04-12T17:53:32Z |
| format | Article |
| id | doaj.art-30c6a3b7dca540f48d4be4e0e3a85520 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-04-12T17:53:32Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-30c6a3b7dca540f48d4be4e0e3a855202022-12-22T03:22:26ZengBMCCancer Cell International1475-28672022-10-0122112010.1186/s12935-022-02746-0LncRNA XIST from the bone marrow mesenchymal stem cell derived exosome promotes osteosarcoma growth and metastasis through miR-655/ACLY signalGuanghui Zhu0Yu Xia1Ziyue Zhao2Aoyu Li3Hui Li4Tao Xiao5Department of Orthopaedics, The Second Xiangya Hospital, Central South UniversityDepartment of Orthopaedics, The Second Xiangya Hospital, Central South UniversityDepartment of Orthopaedics, The Second Xiangya Hospital, Central South UniversityDepartment of Orthopaedics, The Second Xiangya Hospital, Central South UniversityDepartment of Orthopaedics, The Second Xiangya Hospital, Central South UniversityDepartment of Orthopaedics, The Second Xiangya Hospital, Central South UniversityAbstract Background Long non-coding RNA X-inactive specific transcript (XIST) regulates the progression of a variety of tumors, including osteosarcoma. Bone marrow mesenchymal stem cells (BMSCs) can be recruited into osteosarcoma tissue and affect the progression by secreting exosomes. However, whether BMSCs derived exosomes transmit XIST to regulate the growth and metastasis of osteosarcoma and the related mechanism are still unclear. Method In this study, BMSCs derived exosomes were used to treat human osteosarcoma cells MG63 and 143B, and the level of XIST in BMSCs was intervened by siRNA. CCK-8, EdU, transwell assays were used to analyze the changes of cell proliferation, migration and invasion. Bioinformatics analysis, RNA pulldown and dual-luciferase reporter gene assays validated the targeted relationship of XIST with miR-655 and the interaction between miR-655 and ACLY 3’-UTR. 143B/LUC cell line was used to establish an animal model of in situ osteosarcoma to verify the found effects of XIST on osteosarcoma. Oil Red O staining, Western blot and so on were used to detect the changes of lipid deposition and protein expression. Results It was found that BMSCs derived exosomes promoted the proliferation, migration and invasion of osteosarcoma cells, and the down-regulation of XIST inhibited this effect. miR-655 mediated the role of BMSCs derived exosomal XIST in promoting the progression of osteosarcoma and down-regulation of miR-655 could reverse the effects of inhibiting XIST on the proliferation, migration and invasion of osteosarcoma cells. Meanwhile, animal level results confirmed that BMSCs derived exosomal XIST could promote osteosarcoma growth and lung metastasis by combining with miR-655. In-depth mechanism study showed that BMSCs derived exosomal XIST combined with miR-655 to increase the protein level of ACLY, which led to lipid deposition and activate β-catenin signal to promote the proliferation, migration and invasion of osteosarcoma cells. Conclusion This study showed that BMSCs derived exosomal XIST could enter osteosarcoma cells, bind and down-regulates the level of miR-655, resulting in an increase in the level of ACLY, thus increasing the lipid deposition and the activity of β-catenin signal to promote the growth and metastasis of osteosarcoma.https://doi.org/10.1186/s12935-022-02746-0Bone marrow mesenchymal stem cellsOsteosarcomaExosomeLncRNA XISTmiR-655 |
| spellingShingle | Guanghui Zhu Yu Xia Ziyue Zhao Aoyu Li Hui Li Tao Xiao LncRNA XIST from the bone marrow mesenchymal stem cell derived exosome promotes osteosarcoma growth and metastasis through miR-655/ACLY signal Cancer Cell International Bone marrow mesenchymal stem cells Osteosarcoma Exosome LncRNA XIST miR-655 |
| title | LncRNA XIST from the bone marrow mesenchymal stem cell derived exosome promotes osteosarcoma growth and metastasis through miR-655/ACLY signal |
| title_full | LncRNA XIST from the bone marrow mesenchymal stem cell derived exosome promotes osteosarcoma growth and metastasis through miR-655/ACLY signal |
| title_fullStr | LncRNA XIST from the bone marrow mesenchymal stem cell derived exosome promotes osteosarcoma growth and metastasis through miR-655/ACLY signal |
| title_full_unstemmed | LncRNA XIST from the bone marrow mesenchymal stem cell derived exosome promotes osteosarcoma growth and metastasis through miR-655/ACLY signal |
| title_short | LncRNA XIST from the bone marrow mesenchymal stem cell derived exosome promotes osteosarcoma growth and metastasis through miR-655/ACLY signal |
| title_sort | lncrna xist from the bone marrow mesenchymal stem cell derived exosome promotes osteosarcoma growth and metastasis through mir 655 acly signal |
| topic | Bone marrow mesenchymal stem cells Osteosarcoma Exosome LncRNA XIST miR-655 |
| url | https://doi.org/10.1186/s12935-022-02746-0 |
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