The Clinical Significance of IMP3 Expression in Oral Cancer and Its Role in Tumorigenesis and Invasion

We identified insulin-like growth factor II mRNA binding protein 3 (IMP3) as a gene overexpressed in oral squamous cell carcinoma. IMP3 is an RNA-binding protein expressed in multiple fetal tissues and not expressed in adult organs. It was reported to re-expressed in several types of cancer and the expression is frequently associated with high tumor stage and poor prognosis. However, its roles in tumor formation and metastasis have not been proved. In this proposal, we will use tumor samples, in vivo and in vitro tumorigenesis and metastasis assays to prove: (1) IMP3 expression is a prognostic factor in OSCC. (2) IMP3 expression promotes tumor formation. (3) IMP3 expression promotes tumor invasion and metastasis. We will use the following methods to prove our hypothesis: (1) Immunohistochemical staining of IMP3 in 200 OSCC to study the association of IMP3 expression and clinicopathologic factors and patient survival. (2) Establish OSCC cell lines with depletion of IMP3 by si-RNA. Use MTT assay, soft agar assay, and nude mice injection assay to study the effects of expression of IMP3 on cell proliferation, anchorage-independent growth, and tumor formation in mice. (3) Use Boyden chamber invasion assay to study the effect of IMP3 on cell migration and tumor invasion and use nude mice tail vein injection to study the role of IMP3 on tumor metastasis. (4) Identify the mRNA bound to IMP3 by immunoprecipitation-microarray analysis.