title: Knockdown of High Mobility Group-Box 3 (HMGB3) Expression Inhibits Proliferation, Reduces Migration, and Affects Chemosensitivity in Gastric Cancer Cells.
abstract: BACKGROUND High mobility group-box 3 (HMGB3) has been shown to affect tumor initiation and progression. This research aimed to investigate the role of HMGB3 in gastric cancer (GC) cell proliferation, migration, invasion, chemoresistance, and its potential molecular mechanisms. MATERIAL AND METHODS GC MGC803 and BGC823 cells were transfected with siRNA targeting the HMGB3 gene. The expressions of HMGB3 protein in MGC803 and BGC823 cells after transfection were detected by Western blot assays. We detected cell proliferation and cell cycle by MTT and flow cytometry assay. Cell migration and invasion were determined by wound scratch and transwell assay. MGC803 and BGC823 cells were treated with various concentrations of oxaliplatin, cisplatin, and paclitaxel. After 24 hours of drug exposure, we performed MTT assays to investigate chemoresistance in both groups. Western blot assays were used to detect related proteins expression. RESULTS Silencing of HMGB3 inhibited cell proliferation and induced G0/G1 phase arrest of GC cells partly via modulating p53 and p21 pathways, and downregulating Bcl-2/Bax ratio. RNA interference of HMGB3 inhibited cell invasion and migration by downregulating MMP2 and MMP9. Silencing of HMGB3 enhanced sensitive to cisplatin and paclitaxel, and reduced sensitive to oxaliplatin. CONCLUSIONS These findings suggest the importance of HMGB3 in the regulation of growth, migration, and apoptosis of GC, improve our understanding of the mechanisms of GC pathogenesis, and may promote the development of novel targeted therapies.
authors: Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China (mainland).
authors: Shengnan
authors: S
authors: Guo
authors: Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China (mainland).
authors: Yuanyuan
authors: Y
authors: Wang
authors: Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China (mainland).
authors: Yu
authors: Y
authors: Gao
authors: Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China (mainland).
authors: Yinxu
authors: Y
authors: Zhang
authors: Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China (mainland).
authors: Mingzi
authors: M
authors: Chen
authors: Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China (mainland).
authors: Minghao
authors: M
authors: Xu
authors: Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China (mainland).
authors: Lu
authors: L
authors: Hu
authors: Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China (mainland).
authors: Yu
authors: Y
authors: Jing
authors: Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China (mainland).
authors: Fangyu
authors: F
authors: Jing
authors: Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China (mainland).
authors: Chen
authors: C
authors: Li
authors: Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China (mainland).
authors: Qingjun
authors: Q
authors: Wang
authors: Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China (mainland).
authors: Zhitu
authors: Z
authors: Zhu
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D055785:Gene Knockdown Techniques; D025765:HMGB3 Protein / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D014162:Transfection
chemical_list: D025765:HMGB3 Protein; D034741:RNA, Small Interfering