Pro-neural miR-128 is a glioma tumor suppressor that targets mitogenic kinases

Abstract

MicroRNAs (miRNAs) carry out post-transcriptional control of a multitude of cellular processes. Aberrant expression of miRNA can lead to diseases, including cancer. Gliomas are aggressive brain tumors that are thought to arise from transformed glioma-initiating neural stem cells (giNSCs). With the use of giNSCs and human glioblastoma cells, we investigated the function of miRNAs in gliomas. We identified pro-neuronal miR-128 as a candidate glioma tumor suppressor miRNA. Decreased expression of miR-128 correlates with aggressive human glioma subtypes. With a combination of molecular, cellular and in vivo approaches, we characterize miR-128’s tumor suppressive role. miR-128 represses giNSC growth by enhancing neuronal differentiation. miR-128 represses growth and mediates differentiation by targeting oncogenic receptor tyrosine kinases (RTKs) epithelial growth factor receptor and platelet-derived growth factor receptor-α. Using an autochthonous glioma mouse model, we demonstrated that miR-128 repressed gliomagenesis. We identified miR-128 as a glioma tumor suppressor that targets RTK signaling to repress giNSC self-renewal and enhance differentiation.

PBX3 is targeted by multiple miRNAs and is essential for liver tumour-initiating cells

“…PBX3 has been observed to be aberrantly overexpressed in a variety of tumours [54][55][56][57][58] ; however, little is known about its biological roles in tumorigenesis and progression. Our current study demonstrates that PBX3 plays determinant roles in HCC TIC properties, in particularly, controlling directly the expression of TIC surface markers a2d1 and EpCAM, stem cell master genes SOX2 and SALL2, as well as regulating the self-renewal and tumorigenicity potential.…”

p38α Mitogen-Activated Protein Kinase Depletion and Repression of Signal Transduction to Translation Machinery by miR-124 and -128 in Neurons

“…2A) (27,28). Both of these miRNAs were previously proposed to target p38␣ using in silico and in vitro methods (29)(30)(31). Both miR-124/-128 sites are highly conserved in the p38␣ mRNA 3=UTRs of vertebrates (from amphibians to humans) ( Fig.…”

miR-128 downregulation promotes growth and metastasis of bladder cancer cells and involves VEGF-C upregulation

“…MiR-128 is an miRNA that behaves differently according to the tissue or cell background and has been studied extensively in glioma. miR-128 inhibits glioma proliferation and self-renewal by targeting Bmi-1, E2F3a and mitogenic kinases (7)(8)(9). In addition, miR-128 inhibits tumor growth and angiogenesis by targeting p70S6K1 (10), promotes cell-cell adhesion in U87 glioma cells via regulation of EphB2 (11) and modulates glioma progression by regulating the SNAI1, miR-128 and SP1 axis (12).…”