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Jagged1 regulates STAT3 signaling pathway and affects growth and apoptosis of multiple myeloma cells
Authors:ZHANG Xi-hui  GONG Jian  HUANG Sheng  ZHOU Li  XU Ming-kui  ZENG De-bin
Institution:1. Department of Orthopedics II, Hainan Traditional Chinese Medicine Hospital, Haikou 570203, China; 2. Department of Orthopedics in the Aged, The Second Hospital of Tangshan, Tangshan 063000, China; 3. Department of Orthopedics, Affiliated Hospital of Hainan Medical University, Haikou 570102, China; 4. Hand Microsurgery, Hainan Provincial People's Hospital, Haikou 570311, China
Abstract:AIM:To investigate the effect of Jagged1 on the growth and apoptosis of multiple myeloma cells. METHODS:Transfection with small interfering RNA targeting Jagged1 and negative control was carried out in multiple myeloma cell line U266, and the mRNA and protein levels of Jagged1 in the cells were determined by RT-qPCR and Wes-tern blot. The cells without transfection were used as blank control. Trypan blue staining was used to draw the cell growth curve. The cell viability was measured by MTT assay. The apoptosis was analyzed by flow cytometry. The protein levels of STAT3, p-STAT3 and Bax in the cells were determined by Western blot. STAT3 signaling pathway inhibitor AG490 was used to detect the activation level of STAT3 signaling in the cells. RESULTS:Compared with the U266 cells without transfection, the expression of Jagged1 at mRNA and protein levels decreased in the U266 cells transfeced with small interfering RNA targeting Jagged1 (P<0.05). However, the expression of Jagged1 at mRNA and protein levels did not change in the U266 cells transfected with small interfering RNA negative control. Knockdown of Jagged1 expression decreased the cell viability, increased the apoptotic rate, increased Bax levels, and decreased the protein level of p-STAT3 in the U266 cells (P<0.05). AG490 treatment decreased the protein level of p-STAT3, blocked the activation of STAT3 signaling pathway, promoted the cell apoptosis induced by Jagged1 knockdown, and inhibited the viability of the U266 cells. CONCLUSION:Knock-down of Jagged1 expression promotes the apoptosis of multiple myeloma cells by inhibiting STAT3 signaling pathway, thus suppressing cell growth.
Keywords:Multiple myeloma  Jagged1  Apoptosis  Cell growth  STAT3 signaling pathway  
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