MicroRNA-100 Inhibits Migration of Glioblastoma Cancer Stem Cells and Reduces the Nuclear Orphan Receptor Family member 77, Nur77
Bahauddeen M. Alrfaei, Arwa Alsubait and Ahmed Aloraidi
1Stem Cells Unit, King Abdullah International Medical Research Center (KAIMRC) Saudi Arabia.
2King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia.
3Neurosurgery department, King Abdulaziz Medical City, KAIMRC, Ministry of National Guard-Health Affairs, Saudi Arabia.
Glioblastoma multiforme (GBM) is the most fatal and most progressive malignant human glioma. In spite of top and excellent standard of care which include total resection, radiation, and chemotherapy, the median survival did not exceed two years. Many microRNAs (miRNAs) have been reported recently as important for stimulating or restraining GBM growth. We previously demonstrated that GBMs possess low expression levels of miR-100 relative to control tissue and that restoring high expression repressed GBM tumorigenesis. It is also known that cancer stem cells are resistant to conventional therapy. In this project, we report that miR-100 internal expression is low in GBM cancer stem cells (CSCs) for both U87 derived CSCs and patient derived primary CSCs. Rescue miR-100 expression decreased CSCs migration ability in all samples. Furthermore, overexpression of miR-100 reduced Nur77 (nuclear orphan receptor family member 77) protein expression which play a major role migration. This finding may contribute to less tumor propagation and better outcome.
NR4A1/ Nu77; microRNA; miR; GBM stem cells; Tumor initiating cells