Anti-tumoral effects of miR-3189-3p in glioblastoma

Authors

Duane Jeansonne, From the Department of Medicine and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112.
Mariacristina DeLuca, From the Department of Medicine and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112.
Luis Marrero, From the Department of Medicine and.
Adam Lassak, From the Department of Medicine and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112.
Marco Pacifici, From the Department of Medicine and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112.
Dorota Wyczechowska, From the Department of Medicine and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112.
Anna Wilk, From the Department of Medicine and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112.
Krzysztof Reiss, From the Department of Medicine and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112.
Francesca Peruzzi, From the Department of Medicine and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112 fperuz@lsuhsc.edu.

Document Type

Article

Publication Date

3-27-2015

Abstract

Glioblastoma is one of the most aggressive brain tumors. We have previously found up-regulation of growth differentiation factor 15 (GDF15) in glioblastoma cells treated with the anticancer agent fenofibrate. Sequence analysis of GDF15 revealed the presence of a microRNA, miR-3189, in the single intron. We then asked whether miR-3189 was expressed in clinical samples and whether it was functional in glioblastoma cells. We found that expression of miR-3189-3p was down-regulated in astrocytoma and glioblastoma clinical samples compared with control brain tissue. In vitro, the functionality of miR-3189-3p was tested by RNA-binding protein immunoprecipitation, and miR-3189-3p coimmunoprecipitated with Argonaute 2 together with two of its major predicted gene targets, the SF3B2 splicing factor and the guanine nucleotide exchange factor p63RhoGEF. Overexpression of miR-3189-3p resulted in a significant inhibition of cell proliferation and migration through direct targeting of SF3B2 and p63RhoGEF, respectively. Interestingly, miR-3189-3p levels were increased by treatment of glioblastoma cells with fenofibrate, a lipid-lowering drug with multiple anticancer activities. The attenuated expression of miR-3189-3p in clinical samples paralleled the elevated expression of SF3B2, which could contribute to the activation of SF3B2 growth-promoting pathways in these tumors. Finally, miR-3189-3p-mediated inhibition of tumor growth in vivo further supported the function of this microRNA as a tumor suppressor.

Publication Source (Journal or Book title)

The Journal of biological chemistry

First Page

8067

Last Page

80

Recommended Citation

Jeansonne, D., DeLuca, M., Marrero, L., Lassak, A., Pacifici, M., Wyczechowska, D., Wilk, A., Reiss, K., & Peruzzi, F. (2015). Anti-tumoral effects of miR-3189-3p in glioblastoma. The Journal of biological chemistry, 290 (13), 8067-80. https://doi.org/10.1074/jbc.M114.633081