Expression level of miRNAs on chromosome 14q32.31 region correlates with tumor aggressiveness and survival of glioblastoma patients

Shahar, Tal; Granit, Avital; Zrihan, Daniel; Canello, Tamar; Charbit, Hanna; Einstein, Ofira; Rozovski, Uri; Elgavish, Sharona; Ram, Zvi; Siegal, Tali; Lavon, Iris

doi:10.1007/s11060-016-2248-0

Cited by 20 publications

(15 citation statements)

References 48 publications

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“…At present, the treatment of GBM cells mainly depends on chemotherapy, and the increase of drug resistance is a global problem (4). Several studies have revealed that miRNA is involved in the process of glioma resistance (23)(24)(25). Collectively, the present findings demonstrated that miR-181a-5p is a tumor suppressor gene in GBM, potentially providing a theoretical basis for treatment of drug-resistant GBM in clinical practice.…”

Section: Discussionsupporting

confidence: 51%

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miR‑181a‑5p inhibits the proliferation and invasion of drug‑resistant glioblastoma cells by targeting F‑box protein 11 expression

Wen

Guo

et al. 2020

Oncol Lett

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Glioblastoma (GBM) is the most common malignant primary tumor in the human central nervous system. The present study aimed to explore the molecular mechanism by which microRNA (miR)-181a-5p targets the F-box protein 11 (FBXO11) in glioma cells to inhibit cell proliferation and invasion. Reverse transcription-quantitative (RT-q)PCR was performed to detect the expression levels of miR-181a-5p in U251TR cells, U251 cells, primary GBM tissues and relapsed GBM tissues in order to determine the association between miR-181a-5p and the chemoresistance of GBM cells. The expression levels of miR-181a-5p in GBM cells were modulated via transfecting miR-181a-5p mimics and inhibitors. Cell Counting Kit-8 assays were undertaken to assess the effects of miR-181a-5p on drug sensitivity and proliferation of GBM cells. Wound healing assays were performed to examine the effects of miR-181a-5p on the migratory ability of GBM cells. Furthermore, the effects of miR-181a-5p on the invasive ability of GBM cells were analyzed using an in vitro invasion assay. Flow cytometry analysis was carried out to determine whether overexpression of miR-181a-5p can promote the apoptotic rate of GBM cells. RT-qPCR and western blotting were employed to detect the effects of miR-181a-5p on mRNA and protein expression of FBX011. miR-181a-5p exhibited low expression in resistant GBM cell lines and recurrent tumor tissues. Dual-luciferase reporter assays were utilized to detect luciferase activity to verify the targeted regulatory association between miR-181a-5p and FBXO11. Upregulation of miR-181a-5p promoted the sensitivity of GBM cells to temozolomide (TMZ), increased the apoptotic rate of GBM cells and significantly inhibited the invasive and migratory capacities of GBM cells. In drug-resistant glioma cells, compared with the miR-negative control group and the blank group, the expression of miR-181a-5p was significantly upregulated (P<0.01), while the expression of FBXO11 protein was downregulated. miR-181a-5p increased the sensitivity of GBM cells to TMZ. miR-181a-5p significantly inhibited the migratory and invasive capacities of GBM cells. miR-181a-5p may become a novel effective target for the treatment of GBM. The results of dual-luciferase reporter assays indicated that miR-181a-5p could target the 3'-untranslated region of FBXO11. The underlying mechanism may be targeted inhibition of FBXO11 gene expression, or may be associated with apoptosis.

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Section: Discussionsupporting

confidence: 51%

“…miRs are endogenous non-coding RNAs that are 20-25 nucleotides in length. Dysregulation of miRNAs in brain tumors result in chromosomal aberration, epigenetic modifications and mutations (25). miRNAs possess special biological characteristics and an important function (22)(23)(24).…”

Section: Discussionmentioning

confidence: 99%

miR‑181a‑5p inhibits the proliferation and invasion of drug‑resistant glioblastoma cells by targeting F‑box protein 11 expression

Wen

Guo

et al. 2020

Oncol Lett

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“…MGMT Promoter Methylation, and IDH1-R132H mutation testing were performed as previously described [ 22 – 24 ].…”

Section: Methodsmentioning

confidence: 99%

Androgen receptor: a potential therapeutic target for glioblastoma

et al. 2018

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The median survival time of patients with glioblastoma is still poor (14.6 month), partly due to a lack of effective treatment.We have observed that androgen receptor (AR) is amplified in glioblastomas at the DNA, RNA and protein levels. The AR gene was amplified in 27% of glioblastoma specimens from men (n=22) and of 38.2% from women (n=21). AR-RNA was overexpressed (>2.5 fold) in 93% (n=30), and AR-protein was induced (>two fold) in 56% of the glioblastomas samples (n=16). Thirty percent of the glioblastomas (n=21) also expressed a constitutively active AR-splice-variant (AR-V7/AR3) lacking the Ligand-Binding-Domain. Following these findings, we examined the effect of pharmacological inhibition of androgen receptor in vitro and in vivo, as well as of genetic silencing of the receptor in glioblastoma cell lines. AR antagonists, induced concentration-dependent death in three glioblastoma cell lines, as well as in two glioma initiating cell lines. Silencing of AR expression by siRNA induced cell death in the three tested glioblastoma cell lines. Enzalutamide given orally to nude mice bearing subcutaneous human glioma xenografts resulted in a 72% reduction in tumor volume (p=0.0027).The presence of AR-V7/AR3 in glioblastoma, together with the present data showing that genetic silencing of the full length AR in cell lines and pharmacological inhibition of AR, induce GBM cell death in vivo and in vitro, point to the important role of AR in GBM survival and render a potential therapeutic target for this devastating disease.

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“…In addition, increased expression of miR-411 and -1185 has been involved in the pathogenesis of cardiovascular disease [44,45] and miR-495-3p in tumour sensitivity [46]. Decreased expression of miR-299-3p and -369-3p has been linked to tumorigenesis [47,48] and miR-300 to poor prognosis in patients with cancer [49].…”

Section: Discussionmentioning

confidence: 99%

A microRNA expression signature of the postprandial state in response to a high-saturated-fat challenge

López

Bermúdez

Paz

et al. 2018

The Journal of Nutritional Biochemistry

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The postprandial hypertriglyceridemia is an important and largely silent disturbance involved in the genesis of numerous pathological conditions. Exaggerated and prolonged states of postprandial hypertriglyceridemia are frequently related to the ingestion of meals enriched in saturated fatty acids (SFAs). MicroRNAs are noncoding RNAs that function as gene regulators and play significant roles in both health and disease. However, differential miRNA expression between fasting and postprandial states has never been elucidated. Here, we studied the impact of a high-saturated-fat meal, mainly rich in palmitic acid, on the miRNA signature in peripheral blood mononuclear cells (PBMCs) of nine male healthy individuals in the postprandial period by using a two-step analysis: miRNA array and validation through quantitative real-time polymerase chain reaction. Compared with miRNA expression signature in PBMCs at fasting, 36 miRNAs were down-regulated and 43 miRNAs were up-regulated in PBMCs at postprandial hypertriglyceridemic peak. Six chromosomes (3, 7, 8, 12, 14 and 19) had nearly half (48.1%) of dysregulated miRNA-gene-containing regions. Down-regulated miR-300 and miR-369-3p and up-regulated miR-495-3p, miR-129-5p and miR-7-2-3p had the highest number of target genes. The differentially expressed miRNAs and their predicted target genes involved pathways in cancer, MAPK signaling pathway, endocytosis and axon guidance. Only down-regulated miRNAs notably targeted PI3K-Akt signaling pathways, whereas only up-regulated miRNAs targeted focal adhesion, Wnt signaling pathway, transcriptional misregulation in cancer and ubiquitin-mediated proteolysis. This is the first study of miRNA expression analysis of human PBMCs during postprandial hypertriglyceridemia and offers insight into new potential mechanisms by which dietary SFAs influence health or disease.

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Expression level of miRNAs on chromosome 14q32.31 region correlates with tumor aggressiveness and survival of glioblastoma patients

Cited by 20 publications

References 48 publications

miR‑181a‑5p inhibits the proliferation and invasion of drug‑resistant glioblastoma cells by targeting F‑box protein 11 expression

miR‑181a‑5p inhibits the proliferation and invasion of drug‑resistant glioblastoma cells by targeting F‑box protein 11 expression

Androgen receptor: a potential therapeutic target for glioblastoma

A microRNA expression signature of the postprandial state in response to a high-saturated-fat challenge

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