**5. Future prospects**

Over the past decade, our understanding of genetic alterations and the tumor-specific signal pathways in glioma has been made, although this knowledge to date has not been translated into the prognosis of the patients with glioma. However, a better understanding of key pathways associated with gliomagenesis and malignant transformation could promise further improvements in glioma therapy. Maximum safe resection followed by radiotherapy up to a total dose of 60 Gy and TMZ-based chemotherapy have been established as a standard therapy, but new molecular targeting drugs, including small-molecule cell cycle inhibitors and biological and immune-based therapies have begun to yield promising results in clinical studies.

Over the past two decades, miRNAs have emerged as molecules central to glioma biology. miRNAs represent an additional layer of complexity in tumor biology and have been further validated as regulators of processes fundamental to glioma. This field is rapidly changing. Herein, we have reviewed the emerging roles of miRNAs as drivers of glioma formation and progression with a focus on glioma hallmarks. miRNAs may be essential in glioma growth, angiogenesis, invasion, genomic instability, tumor-promoting inflammation, and gliomaspecific metabolism. In recent years, functions of miRNAs in gliomagenesis and microenvir‐ onment have been considerably elucidated, and we have validated the tumor suppressive or oncogenic functions of miRNAs in glioma. Now, we should move toward a next phase involving clinical trials with miRNAs as glioma therapies. For example, miR-34, a tumorsuppressive miRNA that simultaneously downregulates the expressions of MET, PDGFRA, and CDK6 is currently in clinical trials as a directed therapy for advanced solid tumors. In glioma, the restoration of miR-34a can possibly outperform any single targeted agents tailored to those targets. There remain several problems to use miRNAs in glioma therapy. These include not only accumulation of our knowledge of miRNAs' biological functions in glioma, but also the development of new and safe methods for delivery to glioma cells. Although the clinical application of miRNAs in GBM has yet to be realized, we believe the future of glioma therapy could be bright.

In this review, we have also focused on circulating miRNAs of serum, plasma, and CSF in patients with glioma. The use of miRNAs has several limitations, such as the diversity of methodologies that exist for miRNA detection and the small cohort size for the validation steps reported in current studies. Nonetheless, circulating miRNAs may exhibit diagnostic values, the combination of biomarkers may improve the diagnostic accuracy, and the combination of circulating miRNAs and other screening methods may be particularly useful in glioma detection. However, a standard protocol of sample treatment and suitable internal controls should be further established to make the level of detection comparable to that of other methods before miRNA biomarkers are fully utilized in clinical practice.
