miR‑451a suppression of IL‑6R can inhibit proliferation and increase apoptosis through the JAK2/STAT3 pathway in multiple myeloma

Abstract

The IL‑6R/JAK2/STAT3 pathway mediated by interleukin‑6 (IL‑6) plays an important role in the occurrence and development of multiple myeloma (MM), which is associ‑ ated with decreased microRNA‑451a. However, the biological function of microRNA‑451a in MM remains unclear. The bone marrow (BM) of patients with MM was sampled, and the plasma cells were enriched. BM miR‑451a, IL‑6 and IL‑6R levels and Ki‑67 expression intensity were evaluated using reverse transcription‑quantitative PCR, ELISA and flow cytometry, respectively. U266 cell proliferation, viability and apoptosis were measured using BrdU, CCK‑8 and Annexin V/propidium iodide assays, respectively. Total and phospo‑(p‑) JAK2 and p‑STAT3 levels were measured by western blotting. Dual‑luciferase reporter assays were performed to validate the predicted target binding sites. miR‑451a expression was low in patients with MM and was associated with the Revised International Staging System (R‑ISS) stage. IL‑6 concentra‑ tions were significantly higher in patients with MM than in normal controls and were inversely associated with miR‑451a levels (r=‑0.96, P<0.0001). IL‑6R levels were positively corre‑ lated with the R‑ISS stage. miR‑451a was downregulated, and IL‑6R was upregulated in myeloma cell lines. Treatment with an miR‑451a mimic inhibited viability and induced apoptosis in U266 cells. p‑JAK2 and p‑STAT3 levels were significantly lower in mimic‑treated U266 cells than in control cells. Thus, miR‑451a was shown to regulate myeloma cell proliferation and apoptosis via the IL‑6R/JAK2/STAT3 pathway and may be used to predict patient prognosis.