Abstract 3983: MicroRNAs and other small RNA molecules expressed in metastatic and non-metastatic oral squamous cell carcinoma
Authors: Severino Patricia , Oliveira Liliane Santana , Andreghetto Flavia Maziero , Torres Natalia , Curioni Otavio , Cury Patricia Maluf , Toporcov Tatiana Natasha , Paschoal Alexandre Rossi , Durham Alan Mitchell 
Published: August 2015

Small noncoding RNAs are regulatory molecules that play important roles in several aspects of cellular biology. They vary from 18 to 30 nucleotides in length and often act through the inactivation of complementary sequences. A variety of small RNA classes have been identified to date and the list is constantly growing, owing to the advent of new sequencing technologies. Among these molecules, microRNAs are the most extensively studied. They are known to play important roles in human diseases, including cancer. More recently, genome-wide analyses have showed that changes in the expression levels of other small noncoding RNAs are also associated with cancer, with correlations between RNA abundance and disease status. Oral squamous cell carcinoma, associated with chronic tobacco and alcohol consumption, is among the leading cancers in the world. The presence of cervical lymph node metastases is currently its strongest prognostic factor. The possibility to evaluate its metastatic potential is relevant to the clinical and molecular oncologist due to frequent asymptomatic development of such cancer in its early stages. In this study small RNA libraries from 30 oral squamous cell carcinoma samples were sequenced for the identification and quantification of known small RNAs. Samples were divided in two groups: those presenting lymph node metastasis at the time of diagnosis and those that did not present this characteristic. Additionally, plasma of 30 patients was accessed for the presence of microRNAs identified as differentially expressed between metastatic and non-metastatic tumor samples as a means to identify circulating molecules that could be considered potential biomarkers for lymph node metastasis. Global expression patterns of small RNA molecules were not associated with cervical metastases. MiR-21, miR-203 and miR-205 were highly expressed throughout samples, in agreement with their role in epithelial cell biology, but disagreeing with studies correlating these molecules with cancer invasion. Nineteen microRNAs, but no other small RNA class, varied consistently between metastatic and non-metastatic cancer samples, some of which were also detected at corresponding levels in plasma. MiR-31 and miR-130b, known to inhibit several steps in the metastatic process, were over-expressed in non-metastatic samples and the expression of miR-130b was confirmed in plasma of patients presenting non-metastatic oral squamous cell carcinoma. MiR-181 and miR-296 were associated with metastasis but were not detected in plasma. In conclusion, we identified microRNAs linked to the metastatic status in a group of patients diagnosed with oral squamous cell carcinoma, both in tissue and plasma samples. We also demonstrate that other small RNA classes are expressed and should, therefore, be involved and contribute to the metastatic phenotype of this disease.

Citation Format: Patricia Severino, Liliane Santana Oliveira, Flavia Maziero Andreghetto, Natalia Torres, Otavio Curioni, Patricia Maluf Cury, Tatiana Natasha Toporcov, Alexandre Rossi Paschoal, Alan Mitchell Durham. MicroRNAs and other small RNA molecules expressed in metastatic and non-metastatic oral squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3983. doi:10.1158/1538-7445.AM2015-3983