دورية أكاديمية
Exosomal miR-182 derived from bone marrow mesenchymal stem cells drives carfilzomib resistance of multiple myeloma cells by targeting SOX6.
العنوان: | Exosomal miR-182 derived from bone marrow mesenchymal stem cells drives carfilzomib resistance of multiple myeloma cells by targeting SOX6. |
---|---|
المؤلفون: | Long S; Department of Hematology, The Affiliated Hospital of Jinggangshan University, No. 110, Jinggangshan Avenue, Jizhou District, Ji'an, 343000, Jiangxi Province, People's Republic of China. longshifeng1910@163.com., Long S; Department of Hematology, The Affiliated Hospital of Jinggangshan University, No. 110, Jinggangshan Avenue, Jizhou District, Ji'an, 343000, Jiangxi Province, People's Republic of China., He H; Department of Hematology, The Affiliated Hospital of Jinggangshan University, No. 110, Jinggangshan Avenue, Jizhou District, Ji'an, 343000, Jiangxi Province, People's Republic of China., Luo L; Department of Hematology, The Affiliated Hospital of Jinggangshan University, No. 110, Jinggangshan Avenue, Jizhou District, Ji'an, 343000, Jiangxi Province, People's Republic of China., Liu M; Department of Hematology, The Affiliated Hospital of Jinggangshan University, No. 110, Jinggangshan Avenue, Jizhou District, Ji'an, 343000, Jiangxi Province, People's Republic of China., Ding T; Department of Hematology, The Affiliated Hospital of Jinggangshan University, No. 110, Jinggangshan Avenue, Jizhou District, Ji'an, 343000, Jiangxi Province, People's Republic of China. |
المصدر: | Journal of orthopaedic surgery and research [J Orthop Surg Res] 2023 Dec 07; Vol. 18 (1), pp. 937. Date of Electronic Publication: 2023 Dec 07. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 101265112 Publication Model: Electronic Cited Medium: Internet ISSN: 1749-799X (Electronic) Linking ISSN: 1749799X NLM ISO Abbreviation: J Orthop Surg Res Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London : BioMed Central, 2006- |
مواضيع طبية MeSH: | MicroRNAs*/genetics , MicroRNAs*/metabolism , Multiple Myeloma*/drug therapy , Multiple Myeloma*/genetics , Multiple Myeloma*/metabolism , Mesenchymal Stem Cells*/metabolism, Humans ; Oligopeptides/pharmacology ; Cell Proliferation/genetics ; Tumor Microenvironment ; SOXD Transcription Factors/metabolism |
مستخلص: | Background: Multiple myeloma (MM) is a common hematological malignancy. Drug resistance remains to be a major clinical challenge in MM therapy. In this study, we aim to investigate the functional roles of bone marrow mesenchymal stem cells (BMSC)-derived exosomal miR-182 on the carfilzomib resistance of MM and its underlying mechanism. Methods: qRT-PCR and Western blot methods were utilized to confirm the gene or protein expressions. CCK-8 and transwell assays were performed to measure the capabilities of proliferation, migration, and invasion. The molecular interactions were validated through ChIP and Dual luciferase assay. Results: Our findings indicated that miR-182 expression was upregulated in serum, BMSCs and BMSC-derived exosomes from MM patients. Hypoxia-inducible factor-1α (HIF-1α), a key transcriptional factor in tumor microenvironment, could boost miR-182 expression by directly binding to its promoter, thus favoring exosomal secretion. Moreover, exosomal miR-182 from BMSCs could be transferred to MM cells and was able to promote malignant proliferation, metastasis, and invasion, as well as decrease the sensitivity of MM cells against carfilzomib. Additionally, SOX6 was identified as a downstream target of miR-182 in MM cells, and its expression was negatively regulated by miR-182. Rescue experiments proved that loss of SOX6 in MM cells dramatically reversed the promoting roles of BMSC-secreted exosomal miR-182 on proliferation, metastasis, and carfilzomib resistance in MM cells. Conclusion: Collectively, our findings indicated that exosomal miR-182 derived from BMSCs contributed to the metastasis and carfilzomib resistance of MM cells by targeting SOX6. This study sheds light on the pathogenesis of the BMSC-derived exosome containing miR-182 in the malignant behaviors of MM cells and carfzomib resistance. (© 2023. The Author(s).) |
References: | Sci Rep. 2015 Jul 24;5:12495. (PMID: 26205124) Front Immunol. 2022 Apr 04;13:824188. (PMID: 35444652) Cell Death Dis. 2021 Dec 20;13(1):13. (PMID: 34930918) Cell Commun Signal. 2021 Oct 16;19(1):104. (PMID: 34656117) Clin Lymphoma Myeloma. 2009 Aug;9(4):278-88. (PMID: 19717377) Oncotarget. 2016 Sep 13;7(37):60723-60735. (PMID: 27494872) Blood Rev. 2019 Nov;38:100595. (PMID: 31445775) Br Med Bull. 2023 Sep 07;:. (PMID: 37675799) Apoptosis. 2020 Apr;25(3-4):205-216. (PMID: 31938895) Pathol Res Pract. 2019 Nov;215(11):152603. (PMID: 31540771) Onco Targets Ther. 2012;5:237-44. (PMID: 23055749) Br Med Bull. 2021 Jun 10;138(1):58-67. (PMID: 33454750) Int J Mol Sci. 2019 Jul 01;20(13):. (PMID: 31266187) Blood. 2022 Dec 8;140(23):2429-2442. (PMID: 35271699) J Hematol Oncol. 2016 Jun 30;9(1):52. (PMID: 27363832) Exp Ther Med. 2019 Jun;17(6):4741-4747. (PMID: 31105792) Cancer Manag Res. 2019 Apr 02;11:2663-2675. (PMID: 31037034) Mol Med Rep. 2018 May;17(5):6803-6811. (PMID: 29512775) Gene. 2014 Apr 1;538(2):342-7. (PMID: 24447717) Front Oncol. 2020 Nov 05;10:608815. (PMID: 33251153) Pathol Oncol Res. 2021 May 03;27:1609802. (PMID: 34257622) Int J Mol Sci. 2021 Apr 24;22(9):. (PMID: 33923357) FASEB J. 2022 Oct;36(10):e22553. (PMID: 36111980) World J Stem Cells. 2023 May 26;15(5):421-437. (PMID: 37342223) Br Med Bull. 2020 May 15;133(1):79-94. (PMID: 32219416) Immune Netw. 2022 Oct 07;22(6):e49. (PMID: 36627935) Eur Rev Med Pharmacol Sci. 2020 May;24(10):5412-5418. (PMID: 32495876) Cancer Cell Int. 2021 Aug 31;21(1):462. (PMID: 34465330) J Clin Invest. 2016 Apr 1;126(4):1139-43. (PMID: 27035805) Oncotarget. 2016 May 24;7(21):30876-91. (PMID: 27129167) Cell Death Discov. 2022 Apr 14;8(1):202. (PMID: 35422485) Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2017 Jun;25(3):781-785. (PMID: 28641635) Br Med Bull. 2019 Jun 19;130(1):137-147. (PMID: 31066454) Cardiovasc Res. 2019 Jun 1;115(7):1205-1216. (PMID: 30753344) Mol Cancer Res. 2020 Aug;18(8):1218-1231. (PMID: 32366676) Br Med Bull. 2022 Jul 9;142(1):34-43. (PMID: 35488320) Oncol Lett. 2016 Aug;12(2):1197-1203. (PMID: 27446418) Mediators Inflamm. 2021 Nov 02;2021:9972805. (PMID: 34764819) Front Cell Dev Biol. 2022 Mar 01;10:862524. (PMID: 35300408) J Orthop Surg Res. 2021 Oct 24;16(1):637. (PMID: 34689803) J Pathol. 2016 Jun;239(2):162-73. (PMID: 26956697) Cancer Drug Resist. 2019;2:141-160. (PMID: 34322663) Cancer Sci. 2021 Oct;112(10):3995-4004. (PMID: 34310776) Cell Biol Int. 2021 May;45(5):965-975. (PMID: 33372728) |
فهرسة مساهمة: | Keywords: Bone marrow mesenchymal stem cells; Carfzomil resistance; Exosomal miR-182; Multiple myeloma; SOX6 |
المشرفين على المادة: | 0 (MicroRNAs) 72X6E3J5AR (carfilzomib) 0 (Oligopeptides) 0 (SOX6 protein, human) 0 (SOXD Transcription Factors) 0 (Mirn182 microRNA, human) |
تواريخ الأحداث: | Date Created: 20231207 Date Completed: 20231216 Latest Revision: 20231216 |
رمز التحديث: | 20231217 |
مُعرف محوري في PubMed: | PMC10702080 |
DOI: | 10.1186/s13018-023-04399-9 |
PMID: | 38062424 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1749-799X |
---|---|
DOI: | 10.1186/s13018-023-04399-9 |