Silencing Id-1 inhibits lymphangiogenesis through down-regulation of VEGF-C in oral squamous cell carcinoma.
Our previous study demonstrated that overexpression of Id-1 (inhibitor of differentiation/DNA binding) was associated with lymphatic metastasis in human oral squamous cell carcinoma (OSCC). In this study, we further unveiled the association of Id-1 with vascular endothelial growth factor-C (VEGF-C) and peritumoral lymphatic vessel density (PLVD), and the effect of silencing Id-1 on inhibiting lymphangiogenesis in OSCC. We found that Id-1 was associated with VEGF-C (r=0.569, p<0.001) and PLVD (r=0.240, p<0.001) in OSCC. Lentivirus-mediated RNA interference targeting Id-1 in an OSCC cell line Tca8113 resulted in down-regulation of VEGF-C (p=0.003, 0.007). Moreover, when Id-1 was suppressed by injecting Id-1-siRNA-lentivirus into the transplanted tumors in nude mice, VEGF-C was down-regulated (p=0.018) and the PLVD decreased (p=0.001). Our results suggest that Id-1 was correlated with lymphangiogenesis in OSCC. Silencing Id-1 could inhibit lymphangiogenesis through down-regulation of VEGF-C and it might be a promising treatment modality for the lymphatic metastasis of OSCC.
Department of Oral and Maxillofacial Surgery, Qilu Hospital, and Stamatology Research Center, Shandong University, 107#, Wenhua Xi Road, Jinan 250012, PR China.
Zuoqing
Z
Dong
Fengcai
F
Wei
Chengjun
C
Zhou
Tomoki
T
Sumida
Hiroyuki
H
Hamakawa
Yingwei
Y
Hu
Shaohua
S
Liu
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics* / Q000378:metabolism; D042583:Lymphangiogenesis / Q000235:genetics*; D008207:Lymphatic Metastasis; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism*
C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D042582:Vascular Endothelial Growth Factor C