microRNAs (miRNAs) in Glioblastoma Multiforme (GBM)-Recent Literature Review

Abstract

Glioblastoma multiforme (GBM) is the most common, malignant, poorly promising primary brain tumor. GBM is characterized by an infiltrating growth nature, abundant vascularization, and a rapid and aggressive clinical course. For many years, the standard treatment of gliomas has invariably been surgical treatment supported by radio- and chemotherapy. Due to the location and significant resistance of gliomas to conventional therapies, the prognosis of glioblastoma patients is very poor and the cure rate is low. The search for new therapy targets and effective therapeutic tools for cancer treatment is a current challenge for medicine and science. microRNAs (miRNAs) play a key role in many cellular processes, such as growth, differentiation, cell division, apoptosis, and cell signaling. Their discovery was a breakthrough in the diagnosis and prognosis of many diseases. Understanding the structure of miRNAs may contribute to the understanding of the mechanisms of cellular regulation dependent on miRNA and the pathogenesis of diseases underlying these short non-coding RNAs, including glial brain tumors. This paper provides a detailed review of the latest reports on the relationship between changes in the expression of individual microRNAs and the formation and development of gliomas. The use of miRNAs in the treatment of this cancer is also discussed.

Keywords: glioblastoma multiforme; miRNA.

Figure 1

miRNA biogenesis pathway. miRNA genes are transcribed from the sequences encoding them in the genome most often by RNA polymerase II and the resulting pri-miRNA transcripts are subject to modifications of the 5′ (cap) and 3′ (polyadenyl tail) end. They are treated by the Drosha and Pash proteins by cutting out a region with the structure of a hairpin, thanks to which pre-miRNA molecules with a length of about 70 nucleotides are formed. pre-miRNAs are exported from the nucleus by the nuclear transporter exportin 5. In the cytoplasm, pre-miRNA is cut by the Dicer enzyme into double-stranded molecules about 22 nucleotides long. The less thermodynamically stable of the strands is incorporated into the RISC (RNA-induced silencing complex). A high degree of complementarity of the transcript to the RISC-bound miRNA strand results in degradation of the transcript, while partial complementarity inhibits translation.

Figure 2

Oncogenic miRNAs and tumor suppressor miRNAs in glioblastoma multiforme.

Figure 3

The use of miRNA in therapeutic strategies for glioma.