====== miR-7-5p ======

[[miR]]-7-5p has been recognized as a [[tumor suppressor]] involved in multiple [[cancer]]s. However, the biological effects of miR-7-5p in [[TMZ]] resistance have not been illuminated. 

In a study, Jia et al., used [[RNA sequencing]] and high-throughput screening techniques, which revealed that miR-7-5p is significantly downregulated in TMZ resistant [[LN229]] cells (LN229/TMZ-R) compared to control cells (LN229), and low miR-7-5p expression was correlated with recurrence in [[GBM]] patients. Ectopic overexpression of miR-7-5p sensitized LN229/TMZ-R cells to TMZ and suppressed the stemness of [[glioblastoma stem cell]]s (GSCs). Further experiments demonstrated that miR-7-5p exerts its role by directly targeting the 3'-untranslated region of [[Yin Yang 1]] ([[YY1]]). The findings suggest that combinational use of miR-7-5p and TMZ might be a promising therapeutic strategy to increase the long-term drug response in GBM patients
((Jia B, Liu W, Gu J, Wang J, Lv W, Zhang W, Hao Q, Pang Z, Mu N, Zhang W, Guo
Q. MiR-7-5p suppresses stemness and enhances temozolomide sensitivity of
drug-resistant glioblastoma cells by targeting Yin Yang 1. Exp Cell Res. 2018 Dec
23. pii: S0014-4827(18)31071-1. doi: 10.1016/j.yexcr.2018.12.016. [Epub ahead of 
print] PubMed PMID: 30586549.
)).
----
Li et al., aimed to assess the relationship between circ-U2AF1 (CircRNA ID: hsa_circ_0061868) and hsa-mir-7-5p and examine their effects on proliferation, apoptosis, and the metastatic phenotype of glioma cells regulated by neuro-oncological ventral antigen 2 (NOVA2). We found that the expression levels of circ-U2AF1 and NOVA2 were upregulated, while hsa-miR-7-5p was downregulated in human glioma tissues and glioma cell lines. Our data and bioinformatic analysis indicated the association of these molecules with glioma grade, a positive correlation between circ-U2AF1 and NOVA2 expression levels and a negative correlation of hsa-miR-7-5p with both circ-U2AF1 and NOVA2, respectively. In addition, silencing of circ-U2AF1 expression resulted in increased hsa-miR-7-5p expression and decreased NOVA2 expression both in vitro and in vivo. Luciferase assay confirmed hsa-miR-7-5p as a direct target of circ-U2AF1 and NOVA2 as a direct target of hsa-miR-7-5p. Functionally, silencing of circ-U2AF1 inhibits glioma development by repressing NOVA2 via upregulating hsa-miR-7-5p both in vitro and in vivo. Thus, we assumed that circ-U2AF1 promotes glioma malignancy via derepressing NOVA2 by sponging hsa-miR-7-5p. Taken together, we suggest that circ-U2AF1 can be a prognostic biomarker and the circ-U2AF1/hsa-miR-7-5p/NOVA2 regulatory pathway may be a novel therapeutic target for treating gliomas
((Li G, Huang M, Cai Y, Yang Y, Sun X, Ke Y. Circ-U2AF1 promotes human glioma
via derepressing neuro-oncological ventral antigen 2 by sponging hsa-[[miR-7-5p]]. J 
Cell Physiol. 2018 Oct 20. doi: 10.1002/jcp.27591. [Epub ahead of print] PubMed
PMID: 30341906.)).
----
Functional annotation suggested that 15 of the predicted MicroRNA-targeted genes were involved in vascular endothelial growth factor signaling, in which 3 critical MicroRNAs were involved: miR-7-5p, miR-199a-5p, and miR-200b-3p
((Chen Y, Li Z, Shi Y, Huang G, Chen L, Tan H, Wang Z, Yin C, Hu J. Deep
Sequencing of Small RNAs in Blood of Patients with Brain Arteriovenous
Malformations. World Neurosurg. 2018 Jul;115:e570-e579. doi:
10.1016/j.wneu.2018.04.097. Epub 2018 Apr 22. PubMed PMID: 29689389.
)).
----
It was found that miR-7-5p in GBM microvessels was significantly reduced compared with that in normal brain capillaries. In the in vitro experiments, overexpression of miR-7-5p significantly inhibited human umbilical vein endothelial cell proliferation. Forced expression of miR-7-5p in human umbilical vein endothelial cells in vitro significantly reduced the protein level of RAF1 and repressed the activity of the luciferase, a reporter vector carrying the 3'-untranslated region of RAF1. These findings indicate that RAF1 is one of the miR-7-5p target genes. Furthermore, a significant inverse correlation between miR-7-5p expression and RAF1 protein level in GBM microvasculature was found. These data suggest that miR-7-5p functions as a tumor suppressor gene to regulate GBM microvascular endothelial cell proliferation potentially by targeting the RAF1 oncogene, implicating an important role for miR-7-5p in the pathogenesis of GBM. It may serve as a guide for the antitumor angiogenesis drug development
((Liu Z, Liu Y, Li L, Xu Z, Bi B, Wang Y, Li JY. MiR-7-5p is frequently
downregulated in glioblastoma microvasculature and inhibits vascular endothelial 
cell proliferation by targeting RAF1. Tumour Biol. 2014 Oct;35(10):10177-84. doi:
10.1007/s13277-014-2318-x. Epub 2014 Jul 16. PubMed PMID: 25027403.
)).
----
MicroRNAs (MicroRNAs) are frequently dysregulated in glioblastoma (GBM) patients. It has been discovered that highly stable extracellular MicroRNAs circulate in the blood of both healthy individuals and patients. MicroRNAs in serum of patients with GBM and normal controls were analyzed by microarray analysis. The relevant bioinformatic analysis of the predicted target genes (gene ontology, pathway, gene network analysis) were performed. The MicroRNA microarray reveals differentially expressed MicroRNAs in serum between the GBM and normal controls. Of the 752 MicroRNAs, 115 MicroRNAs were upregulated in the GBM group, and 24 MicroRNAs were downregulated (fold change ≥2.0, P<0.01). By further analysis, we found that miR-576-5p, miR-340 and miR-626 were significantly overexpressed, but miR-320, let-7g-5p and miR-7-5P showed significantly low expression in GBM patients. By further bioinformatic analysis, we found that they possibly play important roles in the regulation of glioma signaling pathways. In summary, the six MicroRNAs are significant distinct in the peripheral blood of patients with GBM pathologies. These data suggest that the MicroRNA profile of the peripheral blood may serve as a new biomarker for glioma diagnosis with high specificity and sensitivity
((Dong L, Li Y, Han C, Wang X, She L, Zhang H. MicroRNA microarray reveals specific
expression in the peripheral blood of glioblastoma patients. Int J Oncol. 2014
Aug;45(2):746-56. doi: 10.3892/ijo.2014.2459. Epub 2014 May 22. PubMed PMID:
24858071.
)).

===== References =====