Journal of biochemical and molecular toxicology · 2025
MiR-155-5p Inhibits Multiple Myeloma Cell Malignancy and Tumorigenesis by Targeting JARID2 and Inactivating the TGFβ/SMAD2 Signaling.
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Yuan Yuan, Zhang Tingting, Zhang Pingping, Han Lili, Li Jiajia, Gao Shuxian
Аннотация
Multiple myeloma (MM) is a hematological malignancy characterized by the accumulation of malignant plasma cells in bone marrow and remains largely incurable. The study aimed to investigate the role of miR-155-5p in modulating malignant cellular behavior and tumorigenesis in MM. MiR-155-5p expression in MM tissues and cells was measured by RT-qPCR. In the context of miR-155-5p overexpression, Transwell, wound healing, and CCK-8 assays were conducted to evaluate cell invasion, migration, and viability, respectively. Xenograft tumor models were established to explore the influence of miR-155-5p and JARID2 on tumor growth in vivo. Gene interaction was analyzed using a luciferase reporter assay. Western blot analysis was carried out to quantify protein expression of JARID2 and components involved in the TGFβ/SMAD2 signaling pathway. Experimental results revealed that miR-155-5p expression was significantly diminished in MM cells and tissue samples. Overexpressing miR-155-5p not only suppressed MM cell viability, invasion, and migration but also restrained tumor growth. JARID2 was highly expressed in MM cells and identified as a direct target of miR-155-5p. In MM tissues, miR-155-5p expression was inversely correlated with JARID2 expression. Furthermore, JARID2 overexpression effectively reversed the inhibitory impacts of miR-155-5p on cell malignancy and tumorigenesis. In addition, miR-155-5p inactivated the TGFβ/SMAD2 pathway by negatively regulating JARID2 expression. In conclusion, miR-155-5p inhibits MM cell malignancy and tumorigenesis by targeting JARID2 and inactivating the TGFβ/SMAD2 signaling.