دورية أكاديمية
أعرض في EDS

Exosomal miR-182 derived from bone marrow mesenchymal stem cells drives carfilzomib resistance of multiple myeloma cells by targeting SOX6.

التفاصيل البيبلوغرافية
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).)
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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
الوصف
تدمد:1749-799X
DOI:10.1186/s13018-023-04399-9