miR-144-3p exerts anti-tumor effects in glioblastoma by targeting c-Met.

Abstract

The study aimed to explore the specific function and mechanism of miR-144-3p in glioblastoma (GBM) cells with different phosphatase and tensin homolog (PTEN) phenotypes. We demonstrated that the miR-144-3p level was significantly down-regulated in glioma compared with the non-neoplastic brain tissues, and decreased with ascending grades. The loss of miR-144-3p effectively predicted the decreased overall survival in glioma patients. Interestingly, the expression of MET was up-regulated and inversely associated with miR-144-3p level in glioma tissues. Next, we certified that miR-144-3p specifically bound to MET 3'-untranslated region (3' UTR) and inhibited its expression. miR-144-3p potently repressed GBM cell proliferation and invasion via suppressing MET in vitro and in vivo. In addition, our results showed no difference in malignancy inhibition induced by miR-144-3p in GBM cells with different PTEN phenotypes. miR-144-3p inhibited several survival signaling pathways by targeting MET independent of PTEN status in GBM cells. Over-expression of miR-144-3p inhibited survival capability and increased apoptosis, resulting in enhancement of radiation and temozolomide sensitivity. Our data provide new insights into the potential application of miR-144-3p in GBM therapy by targeting MET and then inhibiting the downstream signaling.

• Authors: Fengming Lan, Huiming Yu, Man Hu, Tingyi Xia, Xiao Yue
• Journal: Journal of neurochemistry (J Neurochem) Vol. 135 Issue 2 Pg. 274-86 (Oct 2015) ISSN: 1471-4159 [Electronic] England
• PMID: 26250785 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 International Society for Neurochemistry.

Chemical References

• 3' Untranslated Regions
• Antineoplastic Agents
• Antineoplastic Agents, Alkylating
• MIRN144 microRNA, mouse
• MicroRNAs
• Radiation-Sensitizing Agents
• Dacarbazine
• Proto-Oncogene Proteins c-met
• PTEN Phosphohydrolase
• Temozolomide

Topics

• 3' Untranslated Regions (genetics)
• Animals
• Antineoplastic Agents (therapeutic use)
• Antineoplastic Agents, Alkylating (therapeutic use)
• Apoptosis (drug effects)
• Brain Neoplasms (drug therapy, genetics)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Dacarbazine (analogs & derivatives, therapeutic use)
• Glioblastoma (drug therapy, genetics)
• Humans
• Mice
• Mice, Nude
• MicroRNAs (genetics)
• PTEN Phosphohydrolase (biosynthesis, genetics)
• Proto-Oncogene Proteins c-met (drug effects)
• Radiation-Sensitizing Agents (pharmacology)
• Survival Analysis
• Temozolomide