title: RUNX3 plays an important role in As2O3‑induced apoptosis and allows cells to overcome MSC‑mediated drug resistance.
abstract: The interaction between bone marrow stromal cells and leukemia cells is critical for the persistence and progression of leukemia, and this interaction may account for residual disease. However, the link between leukemia cells and their environment is still poorly understood. In our study, runt‑related transcription factor 3 (RUNX3) was identified as a novel target gene affected by As2O3 and involved in mesenchymal stem cell (MSC)‑mediated protection of leukemia cells from As2O3‑induced apoptosis. We observed induction of RUNX3 expression and the translocation of RUNX3 into the nucleus after As2O3 treatment in leukemia cells. In K562 chronic myeloid leukemia cells, downregulation of endogenous RUNX3 compromised As2O3‑induced growth inhibition, cell cycle arrest, and apoptosis. In the presence of MSC, As2O3‑induced expression of RUNX3 was reduced significantly and this reduction was modulated by CXCL12/CXCR4 signaling. Furthermore, overexpression of RUNX3 restored, at least in part, the sensitivity of leukemic cells to As2O3. We conclude that RUNX3 plays an important role in As2O3‑induced cellular responses and allows cells to overcome MSC‑mediated drug resistance. Therefore, RUNX3 is a promising target for therapeutic approaches to overcome MSC‑mediated drug resistance.
authors: Renal Transplantation Center, Anhui Provincial Hospital, Hefei, Anhui 230001, P.R. China.
authors: Guo-Zheng
authors: GZ
authors: Pan
authors: School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors: Feng-Xian
authors: FX
authors: Zhai
authors: Department of Hematology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors: Yin
authors: Y
authors: Lu
authors: Department of Hematology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors: Zhi-Gang
authors: ZG
authors: Fang
authors: Department of Hematology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors: Rui-Fang
authors: RF
authors: Fan
authors: Department of Hematology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors: Xiang-Fu
authors: XF
authors: Liu
authors: Department of Hematology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors: Dong-Jun
authors: DJ
authors: Lin
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D050677:Core Binding Factor Alpha 3 Subunit / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism* / Q000628:therapy; D008297:Male; D059630:Mesenchymal Stem Cells; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D010087:Oxides / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D050677:Core Binding Factor Alpha 3 Subunit; D010087:Oxides; C493729:Runx3 protein, human; D000077237:Arsenic Trioxide