Texas Children's Hospital Archives - Page 3 of 3

2017

Young Investigator

Wendy Allen-rhoades, Md

Houston, TX

The role of microRNA-214-3p in pediatric osteosarcoma Despite significant advances, cancer remains the leading cause of disease-associated death among children over 1 year of age in developed countries. Specifically, children with sarcomas that have metastasized or relapsed remain a tremendous clinical challenge with overall survival rates of less than 20%, therefore requiring more thorough investigations into their biology such that novel therapeutic targets can be identified and exploited. Osteosarcoma (OS) is a bone sarcoma that is seen predominantly in children and young adults. The 5-year overall survival has remained largely unchanged for the past 30 years.

We have been studying microRNAs (miRNAs) in OS. MicroRNAs are stable, small non-coding RNA molecules that are implicated in regulating physiologic and pathologic processes, including cancers. In our previous work, we identified four miRNAs that can detect OS using a blood sample. One of the miRNAs in that panel, miR-214-3p, was particularly interesting because we found that miR-214-3p levels differ significantly between metastatic and non-metastatic patients (p=0.016), suggesting an association between metastatic status and miR-214 levels. Further, when patients were stratified by metastatic status at time of diagnosis, we found that low levels of plasma miR-214 predicted a significantly better outcome. In fact, all of the metastatic patients with low levels of miR-214-3p at diagnosis are still alive. Simultaneous reports corroborate our finding on the importance of miR-214-3p in OS. Patients with increased miR-214-3p levels within the tumor is associated with a poor outcome. Despite the mounting evidence of the importance of miR-214-3p in OS, the mechanisms by which it affects tumor formation and progression remain unclear. Therefore, we hypothesize that enhanced tumor expression of miR-214-3p regulates critical molecular, metastatic properties in OS.

The goals of this project are:

To describe tumor characteristics of osteosarcoma when levels of miR-214-3p are perturbed (either increased or decreased levels)
Elucidate the molecular events that are regulated by miR-214-3p which change the tumor forming capability and metastatic spread of osteosarcoma.