High expression of RELM-α correlates with poor prognosis and promotes angiogenesis in gastric cancer.
Accumulating evidence indicates that resistin-like molecule-α (RELM-α) is involved in angiogenesis, while the clinical significance and the exact role of RELM-α in gastric cancer remain obscure. The aim of the present study was to evaluate the clinical significance of RELM-α in gastric cancer, and to investigate its effective mechanisms in order to identify a potential therapeutic target. The expression levels of RELM-α in 92 gastric cancer and adjacent normal tissues were investigated and the relationship between RELM-α expression and the clinicopathological characteristics was explored. To investigate the potential role of RELM-α in gastric cancer cell biological behavior, the cell proliferation, migration and invasion assays were conducted using two gastric cancer cell lines (SGC7901 and MKN45). We also assessed whether RELM-α gene silencing modulates angiogenesis using small interference RNA in cancer cell lines, and investigated its effect on nuclear factor (NF)-κB activation and vascular endothelial growth factor (VEGF) and MMP-9 expression. Contrasting sharply with the strong RELM-α-positive tumors, adjacent normal tissues and cell lines exhibited negative or weakly positive expression (P<0.01). High expression level of RELM-α was associated with advanced stage and tumor size (P<0.01). The silencing of RELM-α expression by Ad5/F35-siRNA treatment significantly inhibited cell migratory and invasive ability in SGC7901 and MKN45 gastric cancer cells compared with the control and Ad5/F35 vector-transfected cell lines (P<0.01). However, the silencing of RELM-α expression also significantly blocked NF-κB activation and attenuated VEGF and MMP-9 expression. The data demonstrated that RELM-α is a promising novel biomarker of angiogenesis in patients with gastric cancer. The study identified that the silencing of RELM-α expression may regulate the proliferation, invasion and migration of gastric cancer cells by targeting VEGF/MMP-9, and the mechanism involved tissue angiogenesis via the NF-κB signaling pathway.
Department of Gastroenterology, Ruijin Hospital North, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
Ping
P
Chen
Department of Laboratory, Second Hospital Affiliated to Lanzhou University, Lanzhou, Gansu 746000, P.R. China.
Deshou
D
Zhao
Department of Gastroenterology, Ruijin Hospital North, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
Weiyi
W
Wang
Department of Gastroenterology, Ruijin Hospital North, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
Yongping
Y
Zhang
Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
Yaozong
Y
Yuan
Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
Lifu
L
Wang
Department of Gastroenterology, Ruijin Hospital North, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
Yunlin
Y
Wu
D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D016328:NF-kappa B / Q000096:biosynthesis; D009361:Neoplasm Invasiveness / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D014408:Biomarkers, Tumor; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B; C486574:RETNLB protein, human; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9