Ying Liu1, Peng Cheng1, Weihua Zhao1, Lihua Zhu2, Jingzhe Sui3, Yi Dai1, Yongrong Lai4. 1. Department of Hematology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China. 2. Department of Health Management, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China. 3. Department of Clinical Laboratory, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China. 4. Department of Hematology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China. Electronic address: laiyongrong@263.net.
Abstract
OBJECTIVE: This study investigated the mechanism by which miR-197-3p regulated IL-6 expression and reduced bortezomib (BTZ) resistance in multiple myeloma (MM). METHODS: The expression of miR-197-3p, MEAF6 and IL-6 in BTZ-resistant MM cells was measured. The effects of miR-197-3p/IL-6 axis on drug resistance and cell apoptosis were evaluated in BTZ-resistant MM cells. The expression of JAK/STAT3 proteins was detected by Western blotting. The binding of miR-197-3p to MEAF6 mRNA was verified using molecular biology techniques. Chromatin immunoprecipitation was used to assess histone acetylation in IL-6 promoter. The effect of miR-197-3p on MM growth was investigated in a mouse model. RESULTS: MiR-197-3p was lowly expressed, and MEAF6 and IL-6 were highly expressed in BTZ-resistant MM cells. Overexpression of miR-197-3p increased drug sensitivity in BTZ-resistant MM cells, which was counteracted by overexpression of IL-6. Overexpression of miR-197-3p also inhibited MM growth in vivo. Mechanistically, miR-197-3p suppressed the expression of IL-6 by inhibiting MEAF6-mediated histone H3 acetylation in IL-6 promoter. The miR-197-3p/IL-6 axis also inhibited the activation of JAK/STAT3 signaling pathway. CONCLUSION: miR-197-3p reduces BTZ resistance in MM by inhibiting acetylation-mediated expression of IL-6 and by inactivating JAK/STAT3 signaling pathway.
OBJECTIVE: This study investigated the mechanism by which miR-197-3p regulated IL-6 expression and reduced bortezomib (BTZ) resistance in multiple myeloma (MM). METHODS: The expression of miR-197-3p, MEAF6 and IL-6 in BTZ-resistant MM cells was measured. The effects of miR-197-3p/IL-6 axis on drug resistance and cell apoptosis were evaluated in BTZ-resistant MM cells. The expression of JAK/STAT3 proteins was detected by Western blotting. The binding of miR-197-3p to MEAF6 mRNA was verified using molecular biology techniques. Chromatin immunoprecipitation was used to assess histone acetylation in IL-6 promoter. The effect of miR-197-3p on MM growth was investigated in a mouse model. RESULTS: MiR-197-3p was lowly expressed, and MEAF6 and IL-6 were highly expressed in BTZ-resistant MM cells. Overexpression of miR-197-3p increased drug sensitivity in BTZ-resistant MM cells, which was counteracted by overexpression of IL-6. Overexpression of miR-197-3p also inhibited MM growth in vivo. Mechanistically, miR-197-3p suppressed the expression of IL-6 by inhibiting MEAF6-mediated histone H3 acetylation in IL-6 promoter. The miR-197-3p/IL-6 axis also inhibited the activation of JAK/STAT3 signaling pathway. CONCLUSION: miR-197-3p reduces BTZ resistance in MM by inhibiting acetylation-mediated expression of IL-6 and by inactivating JAK/STAT3 signaling pathway.