Validation of a rat model for analyzing microRNA in CHONDROSARCOMA
Frisch NB, Evans TJ, Dobson C, Wang Y, Levin AM, Gibson G, Mott MP, and Parsons TW. Validation of a rat model for analyzing microRNA in CHONDROSARCOMA. J Orthop Res 2017; 35
Journal of orthopaedic research
INTRODUCTION: MicroRNA is made up of small non-coding RNA molecules that participate in gene regulation via posttranscriptional gene expression. Certain sequences have been linked to cancer and may be used to predict characteristics of each tumor. However, in order to progress the study of these molecular markers, further study in vivo is required. METHODS: Twenty rats were sacrificed, sterna and rib cartilage were collected, RNA extracted and 233 miRNAs analyzed. The expression of these miRNAs was then compared to their expression in the Swarm rat chondrosarcoma model and in normal human tissue and chondrosarcoma. Interclass correlation coefficient was applied to the data in whole between the rat and human miRNA. RESULTS: For normal human vs normal rat cartilage the interclass correlation coefficient was 0.84 (95% CI: 0.82-0.87). The interclass correlation coefficient for chondrosarcoma in human vs rat tissue was 0.70 (95% CI: 0.65-0.74). A Pearson correlation coefficient was applied to each individual miRNA. The Pearson correlation coefficient for human vs rat chondrosarcoma involving rat tissue from Swarm rat chondrosarcoma samples prior to implantation was 0.174 (p = 0.55). The Pearson correlation coefficient for human vs rat chondrosarcoma for those samples isolated after harvesting tissue from the Swarm rats was 0.168 (p = 0.09). Our findings suggest that human and rat normal cartilage, as well as chondrosarcoma genetics, are sufficiently similar for use of rat models to study chondrosarcoma (interclass correlation coefficient values > 0.70). We also revealed similarities between specific miRNA, especially those with the most similar fold-change (miR26b, 126, 145, 195, and 320). DISCUSSION: At present time, the similarities in miRNA between normal human and rat samples, and human and rat chondrosarcoma samples suggest that the rat model is a viable model for further study of chondrosarcoma and will enable us to determine the role of miRNAs in chondrosarcoma development and progression.