Glioblastoma and MiRNAs

Abstract

Glioblastoma (GB) is one of the most common types of lethal brain tumors. Although several treatment options are available including surgery, along with adjuvant chemo and radiotherapy, the disease has a poor prognosis and patients generally die within 14 months of diagnosis. GB is chemo and radio resistant. Thus, there is a critical need for new insights into GB treatment to increase the chance of therapeutic success. This is why microRNA (miRNA) is being potentially considered in the diagnosis and treatment of glioblastoma. The objective of our review is to provide a holistic picture of GB up-regulated and down-regulated miRNA, in relationship with the expression of other genes, cell signaling pathways, and their role in GB diagnosis and treatment. MiRNA treatment is being considered to be used against GB together with radiotherapy and chemotherapy. Moreover, the use of miRNA as a diagnostic tool has also begun. Knowing that miRNAs are isolated in almost all human body fluids and that there are more than 3000 miRNAs in the human genome, plus the fact that each miRNA controls hundreds of different mRNAs, there is still much study needed to explore how miRNAs relate to GB for its proliferation, progression, and inhibition.

Keywords: diagnosis; glioblastoma; miRNA; treatment.

Figure 1

MicroRNA maturation and function: first, synthesis of double strand primary miRNA occurs in the nucleus with the help of RNA polymerase 2. Then primary RNA undergoes modification with the help of a microprocessing complex containing DROSHA and DGCR8 to form precursor miRNA. This precursor miRNA is further transported to cytosol with the help of exportin 5, and thereafter it is cleaved to a smaller fragment. Finally, the smaller double helix miRNA fragment is released to the single helix miRNA and further commanded by the RISC (RNA-induced silencing complex) to degrade or inhibit the target mRNA.

Figure 2

MiRNAs down-regulate glioblastoma: various miRNAs including miR-302-367, miR-Cdh4, miR-378a-3p, miR-342, miR-153, miR-940, miR-7-5P, miR-101, and miR-338 inhibit different cell signaling networks, transcription factors, and anti-apoptotic genes to inhibit glioblastoma growth.

Figure 3

MicroRNAs up-regulate glioblastoma: various miRNAs such as miR-183, miR-135b, miR-221, miR-222, miR-4443, miR-422a, miR-494-3P, miR-502-5P, miR-520f-3p, miR-549, and miR-223 are responsible for the up-regulation of glioblastoma growth.

Figure 4

MiRNAs down-regulate glioblastoma: miRNAs such as miR-338, miR-181, miR-152-3p, miR-1, miR-212-3p, miR-451, miR-504, and miR-365 regulate the inhibition of glioblastoma through different pathways including those of the PKM2/β-catenine, P13K/Akt, AMPK (AMP-activated protein kinase), Wnt-β-catenine, and PIK3R3.

Figure 5

MicroRNA regulation on glioblastoma: various miRNAs such as miR-7 and miR-362 are responsible for the down-regulation of glioblastoma growth. Although, various miRNAs such as miR-15a-5p, miR-155-3p, miR-522-3p, miR-191, and miR-640 are responsible for the up-regulation of glioblastoma growth.