Abstract 4182: microRNA-29 family as tumor suppressive microRNAs in head and neck squamous cell carcinoma: microRNA-29a/b/c inhibits cell migration and invasion targeting focal adhesion and ECM pathways.
Authors: Nohata Nijiro , Hanazawa Toyoyuki , Kinoshita Takashi , Kikkawa Naoko , Yamamoto Noriko , Yoshino Hirofumi , Itesako Toshihiko , Enokida Hideki , Nakagawa Masayuki , Okamoto Yoshitaka , Seki Naohiko 
Published: August 2014

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. In spite of considerable advances in multimodality therapy such as surgery, radiation therapy and chemotherapy, the overall five-year survival rate for patients with HNSCC is around 40%. Understanding of the molecular cancer pathway underlying HNSCC could significantly improve diagnosis, therapy, and disease prevention. Our microRNA (miRNA) expression signatures of hypopharyngeal squamous cell carcinoma (SCC), and maxillary sinus SCC revealed that the expression of microRNA-29 family (miR-29a/b/c) was significantly reduced in cancer tissues. The aim of the study was to investigate the functional significance of miR-29a/b/c and to explore the novel molecular pathways and responsibility genes regulated by miR-29a/b/c in HNSCC.

METHODS: Gain-of-function studies were performed to investigate cancer cell proliferation, migration and invasion by mature miRNAs transfection into HNSCC cell lines (SAS and FaDu). To identify the biological processes or pathways potentially regulated by the miR-29 family, we applied genome-wide gene expression analysis and in silico study; TargetScan database [http://www.targetscan.org/] and GENECODIS software, which assigned a number of the putative miRNA targets to known pathways in KEGG [http://www.genome.jp/kegg/pathway.html]. The expression levels of miR-29-family target genes were verified using public database of Gene Expression Omnibus (GEO) in HNSCC clinical specimens.

RESULTS: Expression levels of miR-29 family were significantly reduced in HNSCC clinical specimens compared to adjacent non-cancerous tissues (P&lt;0.05). Restoration of each miR-29 family significantly inhibited cancer cell proliferation, migration, and invasion in the HNSCC cell lines. Our expression and in silico analysis showed that miR-29 family appeared to be an important modulator of tumor cell processes through suppression of many targets, particularly those involved in “focal adhesion” and “ECM (extra-cellular matrix)-receptor interaction” signaling pathways (P&lt;0.05). Among two pathways, seven genes were putative targets regulated by miR-29 family (CAV2, CDC42, ITGA6, LAMC1, COL4A1, LAMC2, and COL6A1). Gene expression data showed that three genes (ITGA6, COL4A1 and LAMC2), were significantly up-regulated in clinical HNSCC tumor specimens compared with normal epithelium.

CONCLUSIONS: miR-29 family functioned as pivotal suppressor of cell migration and invasion in HNSCC through targeting “focal adhesion” and “ECM” signaling pathways. Elucidation of tumor suppressive miR-29 family-mediated cancer pathways and putative targets might be provided the novel molecular mechanisms to understand local tumor recurrence or distant metastasis of HNSCC.

Citation Format: Nijiro Nohata, Toyoyuki Hanazawa, Takashi Kinoshita, Naoko Kikkawa, Noriko Yamamoto, Hirofumi Yoshino, Toshihiko Itesako, Hideki Enokida, Masayuki Nakagawa, Yoshitaka Okamoto, Naohiko Seki. microRNA-29 family as tumor suppressive microRNAs in head and neck squamous cell carcinoma: microRNA-29a/b/c inhibits cell migration and invasion targeting focal adhesion and ECM pathways. [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 4182. doi:10.1158/1538-7445.AM2013-4182