Potential of the tumor‑derived extracellular vesicles carrying the miR‑125b‑5p target TNFAIP3 in reducing the sensitivity of diffuse large B cell lymphoma to rituximab
- Li Zhang
- Shixia Zhou
- Tiejun Zhou
- Xiaoming Li
- Junling Tang
Affiliations: Department of Oral and Maxillofacial Surgery, The Affiliated Stomatology Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Department of Hematology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
- Published online on: April 21, 2021 https://doi.org/10.3892/ijo.2021.5211
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Diffuse large B‑cell lymphoma (DLBCL) is the most common and aggressive form of non‑Hodgkin's lymphoma. Extracellular vesicles (EVs) derived from cancer cells are known to modify the tumor microenvironment. The aim of the present study was to investigate the role of miR‑125b‑3p carried by EVs in DLBCL in vitro and in vivo. TNFAIP3 expression in patient lesions was measured and the upstream miR that regulates TNFAIP3 was predicted using the starBase database. EVs were isolated from DLBCL cells and identified. DLBCL cells were transfected with pcDNA to overexpress TNFAIP3 or inhibit miR‑125b‑5p expression, incubated with EVs, and treated with rituximab to compare cell growth and TNFAIP3/CD20 expression. DLBCL model mice were administered EVs, conditioned medium, and rituximab to observe changes in tumor size, volume, and weight. TNFAIP3 was downregulated in patients with DLBCL and its levels further decreased in patients with drug‑resistant DLBCL. Overexpression of TNFAIP3 in DLBCL cells enhanced the inhibitory effect of rituximab and increased CD20 expression. miR‑125b‑5p targeted TNFAIP3. Inhibition of miR‑125b‑5p enhanced the inhibitory effect of rituximab in DLBCL cells. The EV‑carried miR‑125b‑5p reduced the sensitivity of DLBCL cells to rituximab, which was averted by overexpression of TNFAIP3. EVs reduced the sensitivity of DLBCL model mice to rituximab via the miR‑125b‑5p/TNFAIP3 axis. The study findings indicate that the tumor‑derived EVs carrying miR‑125b‑5p can enter DLBCL cells and target TNFAIP3, thus reducing the sensitivity of DLBCL to rituximab, which may provide a novel therapeutic approach for DLBCL.