Transcription Factor IRX5 Promotes TSCC Growth by Targeting OPN/NF-κB
Objectives: Iroquois homeobox gene 5 (Irx5) is a highly-conserved member of the Iroquois homeobox gene family. Members of this family play distinct and overlapping roles in normal embryonic cell patterning and development of malignancies. Our study aims to investigate the role and the mechanism of IRX5 in tongue squamous cell carcinoma (TSCC). Methods: The expression level of IRX5 was examined by qRT-PCR, IHC and western blot. In particular, Cal27 cell line was selected for subsequent experiments, in which the expression level of IRX5 was the most significant. Meanwhile, the effects of IRX5 on proliferation, migration and invasion of TSCC cells were investigated using gain- and loss-of function tools with CCK-8, scratch and transwell assay. Furthermore, bioinformatic analysis and the dual-luciferase reporter assay both were conducted to identify the target of IRX5 in TSCC. In vivo function of IRX5 was detected using xenograft tumor mice model. Results: IRX5 was abnormally abundant in TSCC tissues and cell lines. Elevated levels of IRX5 promoted proliferation, migration and invasion of TSCC cells, whereas stable or transient knockdown of IRX5 expression suppressed TSCC cell proliferation, migration and invasion. As a transcription factor, IRX5 performed this function by targeting osteopontin (OPN) promoter and activating the NF-κB pathway. siRNA targeting OPN and Bay 11-7082 (an inhibitor of NK-κB) reversed the effect of IRX5 overexpression on cal27 behaviour. Finally, studies in xenograft tumor model showed that IRX5 significantly enhanced OPN expression and promoted tumor growth. Conclusions: Taken together, our study elucidates a crucial effect for IRX5 as oncogene in TSCC through the connection with OPN and NK-κB. These findings reveal the new molecular mechanism of IRX5, which may potentiate its use as a novel molecular therapy target for TSCC.
Division: IADR/PER General Session
Meeting:2018 IADR/PER General Session (London, England) Location: London, England
Year: 2018 Final Presentation ID:1090 Abstract Category|Abstract Category(s):Oral Medicine & Pathology Research
Authors
Song, Fangfang
( Wuhan univerisity School & Hospital of Stomatology
, Wuhan
, Hubei
, China
)
Huang, Liyuan
( Wuhan university
, Wuhan
, China
)
Huang, Cui
( Wuhan University
, Wuhan
, China
)
Financial Interest Disclosure: NONE
SESSION INFORMATION
Poster Session
Head and Neck Cancer: Oncogenesis, Invasion and Progression I
Thursday,
07/26/2018
, 11:30AM - 12:45PM