miR-137 acts as a tumor suppressor in astrocytoma by targeting RASGRF1

Tumour Biol. 2016 Mar;37(3):3331-40. doi: 10.1007/s13277-015-4110-y. Epub 2015 Oct 6.


Astrocytoma is one of the most common primary central nervous system tumors and has both high mortality and a poor 5-year survival rate. MicroRNAs (miRNAs) play important roles in carcinogenesis by acting on multiple signaling pathways. Although we have demonstrated that miR-137 is downregulated in astrocytoma tissues, the role of miR-137 in astrocytoma still remains unknown. In the present study, we aimed to investigate the function of miR-137 and its possible target genes in astrocytoma. miR-137 was significantly downregulated in astrocytoma tissues, and its expression level was inversely correlated with the clinical stage. Restoring miR-137 was able to dramatically inhibit cell proliferation, migration, and invasion and enhance apoptosis in vitro, whereas silencing its expression inhibited these processes. By overexpressing or inhibiting miR-137 in cancer cells, we experimentally confirmed that miR-137 directly recognized the 3'-UTR (3'-untranslated region) of the RASGRF1 (Ras protein-specific guanine nucleotide-releasing factor 1) transcript and regulated RASGRF1 expression. Furthermore, an inverse correlation was observed between miR-137 levels and RASGRF1 protein levels, but not mRNA levels, in astrocytoma samples. The silencing of RASGRF1 resulted in similar effects to miR-137 restoration in cancer cells. Finally, overexpression of RASGRF1 rescued the inhibitory effects of miR-137. Taken together, our results indicate that miR-137 acts as a tumor suppressor in astrocytoma by targeting RASGRF1. These findings suggest that miR-137 may serve as a novel therapeutic target in astrocytoma treatment.

Keywords: Apoptosis; Invasion; Migration; Proliferation; RASGRF1; miR-137.

MeSH terms

  • 3' Untranslated Regions / genetics*
  • Apoptosis / genetics
  • Astrocytoma / genetics*
  • Astrocytoma / metabolism
  • Astrocytoma / pathology
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Reverse Transcriptase Polymerase Chain Reaction
  • ras-GRF1 / genetics*
  • ras-GRF1 / metabolism


  • 3' Untranslated Regions
  • MIRN137 microRNA, human
  • MicroRNAs
  • RASGRF1 protein, human
  • ras-GRF1