Abstract 3152: Molecular networks regulated by tumor suppressive microRNA-1 and microRNA-133a in head and neck squamous cell carcinoma

Abstract

Abstract (Background) Head and neck squamous cell carcinomas (HNSCC) represent 6% of all cancers. Despite of considerable advances in surgery, radiotherapy and chemotherapy, the overall 5-year survival rate for patients is less than 40% in advanced stage. The understanding of the new molecular networks of HNSCC oncogenesis by recent genome analysis would be helpful in improving diagnosis and therapy of the disease. Our expression signatures of human cancer including HNSCC revealed that the expression of microRNA-1 (miR-1) and microRNA-133a (miR-133a) were significantly reduced in cancer cells. In human genome, miR-1 and miR-133a located same chromosomal regions (miR-1-2 and miR-133a-1 on 18q11.2, and miR-1-1 and miR-133a-2 on 20q13.33) called cluster. Previously, our group reported that miR-1 and miR-133a function as tumor suppressors in several types of cancers including HNSCC. In this study, we identify the novel molecular networks regulated by miR-1 and miR-133a commonly in HNSCC. (Methods) Genome-wide gene expression analysis was performed to identify the molecular networks of miR-1 and miR-133a by microarray technique. A luciferase reporter assay was used to identify the actual binding site between miR-1 and miR-133a and these candidate target genes. Cell proliferation, migration and invasion assays were performed to investigate the functional significance of target genes in HNSCC cell lines. (Results) Genome-wide molecular targets search and luciferase reporter assay showed that transgelin-2 (TAGLN2), prothymosin-alpha (PTMA) and purine nucleoside phosphorylase (PNP) were directly regulated by miR-1 and miR-133a commonly. Silencing of these genes studies demonstrated significant inhibition of cell proliferation, migration and invasion in HNSCC cells. (Conclusions) TAGLN2, PTMA and PNP were directly regulated by tumor suppressive miR-1 and miR-133a commonly. These genes may function as oncogenes contributed to cell proliferation, migration and invasion in HNSCC. Tumor suppressive miR-1 and miR-133a and target oncogenes may provide new insights into the mechanisms in cancer. Our findings have therapeutic implications and may be exploited for future HNSCC treatments. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3152. doi:1538-7445.AM2012-3152