title: High mobility group box 1/toll-like receptor 4/myeloid differentiation factor 88 signaling promotes progression of gastric cancer.
abstract: High mobility group box 1 and toll-like receptor 4/myeloid differentiation factor 88 signaling pathway have been indicated to have oncogenic effects in many cancers. However, the role of high mobility group box 1/toll-like receptor 4/myeloid differentiation factor 88 signaling pathway in the development of gastric cancer remains unclear. In this study, we demonstrated that high mobility group box 1, toll-like receptor 4, and myeloid differentiation factor 88 were overexpressed in gastric cancer tumors compared with the adjacent non-tumor tissues. The overexpression of high mobility group box 1, toll-like receptor 4, and myeloid differentiation factor 88 were correlated with tumor-node-metastasis stage (p = 0.0068, p = 0.0063, p = 0.0173) and lymph node metastasis (p = 0.0272, p = 0.0382, and p = 0.0495). Furthermore, we observed that knockdown of high mobility group box 1 by high mobility group box 1-small interfering RNA suppressed the expression of toll-like receptor 4 and myeloid differentiation factor 88. Blockage of high mobility group box 1/toll-like receptor 4/myeloid differentiation factor 88 signaling by high mobility group box 1-small interfering RNA resulted in elevation of apoptotic ratio and inhibition of cell growth, migration, and invasion by upregulating Bax expression and downregulating Bcl-2, matrix metalloproteinase-2, nuclear factor kappa B/p65 expression, and the nuclear translocation of nuclear factor kappa B/p65 in gastric cancer cells. Our findings suggest that high mobility group box 1/toll-like receptor 4/myeloid differentiation factor 88 signaling pathway may contribute to the development and progression of gastric cancer via the nuclear factor kappa B pathway and it also represents a novel potential therapeutic target for gastric cancer.
authors.affiliation: 1 Department of Gastroenterology, Qilu Hospital, School of Medicine, Shandong University, Jinan, China.
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Yue
authors.affiliation: 1 Department of Gastroenterology, Qilu Hospital, School of Medicine, Shandong University, Jinan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhou
authors.affiliation: 1 Department of Gastroenterology, Qilu Hospital, School of Medicine, Shandong University, Jinan, China.
authors.forename: Yanjing
authors.initials: Y
authors.lastname: Gao
authors.affiliation: 2 Department of Hepatobiliary Surgery, Qilu Hospital, School of Medicine, Shandong University, Jinan, China.
authors.forename: Zongli
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: 3 Department of Pathology, Qilu Hospital, School of Medicine, Shandong University, Jinan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: 3 Department of Pathology, Qilu Hospital, School of Medicine, Shandong University, Jinan, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: 4 Department of Gastroenterology, Dezhou People's Hospital, School of Medicine, Binzhou Medical University, Dezhou, China.
authors.forename: Wenna
authors.initials: W
authors.lastname: Shi
authors.affiliation: 1 Department of Gastroenterology, Qilu Hospital, School of Medicine, Shandong University, Jinan, China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Su
authors.affiliation: 1 Department of Gastroenterology, Qilu Hospital, School of Medicine, Shandong University, Jinan, China.
authors.forename: Baoquan
authors.initials: B
authors.lastname: Cheng
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D018450:Disease Progression; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism
chemical_list: D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; C498143:RELA protein, human; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA
keywords: High mobility group box 1; gastric cancer; invasion; myeloid differentiation factor 88; proliferation; toll-like receptor 4