Abstract 4171: Tumor suppressive microRNA-218 mediated focal adhesion pathways in cervical squamous cell carcinoma.

Background: MicroRNAs (miRNAs), a class of small non-coding RNAs, regulate protein-coding gene expression by repressing translation or cleaving RNA transcripts in a sequence-specific manner. A growing body of evidence suggests that miRNAs contribute to cervical squamous cell carcinoma (cervical-SCC) progression, development, and metastasis. Recent our miRNA expression signature of SCC (hypopharyngeal-SCC and esophageal-SCC) revealed that microRNA-218 (miR-218) was significantly reduced in cancer tissues. The study of the aim was to investigate the functional significance of miR-218 and its mediated molecular pathways in cervical-SCC. Methods: Gain-of-function studies were performed to investigate cancer cell proliferation, migration and invasion by restoration of mature miRNAs into HPV positive or negative cervical-SCC cell lines (CaSKi, HeLa, ME180 and YUMOTO). To identify the biological processes or pathways potentially regulated by the miRNAs, we applied genome-wide gene expression analysis and in silico study. The GENECODIS software assigned a number of the putative miRNA targets to known pathways in KEGG [http://www.genome.jp/kegg/pathway.html]. Gene expression analyses of all candidate genes involved in each of the pathways using GEO (http://www.ncbi.nlm.nih.gov/geo/) database. Results: Expression levels of miR-218 were significantly reduced in cervical-SCC clinical specimens compared to adjacent non-cancerous tissues (P Conclusions: Aberrant expression of miRNAs has shed light on recent miRNA signatures and identification of tumor suppressive miRNA mediated novel molecular pathways in cervical-SCC. Tumor suppressive miR-218-mediated novel molecular pathways provide a new insight of cervical-SCC oncogenesis and metastasis. Citation Format: Noriko Yamamoto, Takashi Kinosita, Nijiro Nohata, Toshihiko Idesako, Hirofumi Yoshino, Hideki Enokida, Masayuki Nakagawa, Makio Syozu, Naohiko Seki. Tumor suppressive microRNA-218 mediated focal adhesion pathways in cervical squamous cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4171. doi:10.1158/1538-7445.AM2013-4171