title: PGC-1α integrates glucose metabolism and angiogenesis in multiple myeloma cells by regulating VEGF and GLUT-4.
abstract: Human peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) is a key coactivator in the regulation of gene transcriptional activity in normal tissues. However, it is not clear whether it is involved in the angiogenesis and metabolism of multiple myeloma (MM). The aim of the present study was to investigate the role of PGC-1α in MM. Small interfering RNA (siRNA) was used to inhibit PGC-1α expression in RPMI-8226 cells. An endothelial cell migration assay was performed using transwell chambers and the expression of PGC-1α, estrogen-related receptor-α (ERR-α), vascular endothelial growth factor (VEGF) and glucose transporter-4 (GLUT-4) was tested by reverse transcription-polymerase chain reaction (RT-PCR). The protein expression of PGC-1α, ERR-α and GLUT-4 was assayed by western blot analysis. Lastly, RPMI-8226 cell proliferation was evaluated using CCK-8 assay. VEGF and GLUT-4 mRNA levels were decreased in cells treated with siRNA targeting PGC-1α, as was the level of GLUT-4 protein. Endothelial cell migration was significantly reduced when these cells were cultured with culture medium from RPMI-8226 cells treated with siPGC-1α. The proliferation rates at 24 and 48 h were suppressed by PGC-1α inhibition. Our results showed that inhibition of PGC-1α suppresses cell proliferation probably by downregulation of VEGF and GLUT-4. The present study suggests that PGC-1α integrates angiogenesis and glucose metabolism in myeloma through regulation of VEGF and GLUT-4.
authors.affiliation: Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China.
authors.forename: Dedong
authors.initials: D
authors.lastname: Cao
authors.affiliation: Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China.
authors.forename: Jikai
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China.
authors.forename: Han
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Guo
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009101:Multiple Myeloma; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D005947:Glucose; D051275:Glucose Transporter Type 4; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011960:Receptors, Estrogen; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D000097983:ERRalpha Estrogen-Related Receptor; C486497:PPARGC1A protein, human; C495692:SLC2A4 protein, human; C467484:VEGFA protein, human