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Published on: June 16, 2013
Exosomal tRF-1003 induces angiogenesis via regulating the HIF1α/VEGF signaling in multiple myeloma
Yunfeng Fu1, Jianyao Sang2, Fangrong Zhang3
1Department of Blood Transfusion, The Third Xiangya Hospital of Central South University, Changsha 410000, China; Department of Hematology, The Third Xiangya Hospital of Central South University, Changsha 410000, China.
Background:
Multiple myeloma (MM) remains a therapeutically challenging hematologic malignancy characterized by frequent relapse and disease progression. Angiogenesis regulated by non-coding RNAs plays a vital role in MM pathogenesis. Despite the potential clinical applications of tsRNAs, the specific mechanisms by which they contribute to MM progression, particularly through angiogenesis within the bone marrow microenvironment, remain elusive.
Methods:
In this study, we focused on the role of exosomal tRF-1003 in MM progression. Serum and bone marrow samples from relapsed and refractory multiple myeloma (R/RMM) and newly diagnosed multiple myeloma (NDMM) patients were analyzed for tsRNA expression. Functional assays, including transwell migration, wound-healing assays, and in vivo tumor formation studies, were employed to assess the angiogenic potential of tRF-1003 in HUVEC. Mechanistic studies were conducted to understand how tRF-1003 modulates the HIF-1α/VEGF signaling pathway through interaction with MAPK1.
Results:
We found that tRF-1003 was significantly upregulated in serum exosomes derived from R/RMM patients. Exosomal tRF-1003 was efficiently delivered to endothelial cells, leading to enhanced angiogenesis both in vitro and in vivo. Mechanistically, tRF-1003 was shown to activate HIF-1α/VEGF signaling in endothelial cells by downregulating MAPK1 expression, thereby promoting angiogenesis. Overexpression of MAPK1 in endothelial cells partially reversed the angiogenic effects induced by exosomal tRF-1003.
Conclusion:
Our findings reveal that exosomal tRF-1003 plays a pivotal role in MM angiogenesis by modulating the HIF-1α/VEGF signaling pathway through MAPK1. These insights provide a novel perspective on the mechanisms driving MM progression and highlight the potential therapeutic value of targeting tRF-1003 in managing multiple myeloma.
