Navigating the genomic instability mine field of osteosarcoma to better understand implications of non-coding RNAs

Osteosarcoma is one of the most genomically complex cancers and as result, it has been difficult to assign genomic aberrations that contribute to disease progression and patient outcome consistently across samples. One potential source for correlating osteosarcoma and genomic biomarkers is within the non-coding regions of RNA that are differentially expressed. However, it is unsurprising that a cancer classification that is fraught with genomic instability is likely to have numerous studies correlating non-coding RNA expression and function have been published on the subject. This review undertakes the formidable task of evaluating the published literature of noncoding RNAs in osteosarcoma. This is not the first review on this topic and will certainly not be the last. The review is organized with an introduction into osteosarcoma and the epigenetic control of gene expression before reviewing the molecular function and expression of long non-coding RNAs, circular RNAs, and short non-coding RNAs such as microRNAs, piwi RNAs, and short-interfering RNAs. The review concludes with a review of the literature and how the biology of non-coding RNAs can be used therapeutically to treat cancers, especially osteosarcoma. We conclude that non-coding RNA expression and function in osteosarcoma is equally complex to understanding the expression differences and function of coding RNA and proteins; however, with the added lens of both coding and non-coding genomic sequence, researchers can begin to identify the patterns that consistently associate with aggressive osteosarcoma.