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Photomicrographs showing representative results of immunohistochemical analysis of E2F1 expression in specimens of human gliomas of different grades and NATs. a NAT specimen. b, c Grade II glioma specimens. d, e Grade IV glioma specimens. Original magnification ?400. Scale bars were 25 ?m. f Graphical representation of the immunohistochemical analysis in (a?e). Data were presented as mean?SEM. **indicates P<0.001
Source publication
MicroRNAs are single-stranded small non-coding RNA molecules which regulate mammalian cell growth, differentiation, and apoptosis by altering the expression of other genes and play a role in tumor genesis and progression. MiR-106a is upregulated in several types of malignancies and provides a pro-tumorigenic effect. However, its role in glioma is l...
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Context 1
... also examined the protein levels and mRNA expression of E2F1 in human glioma specimens of different WHO grades by immunohistochemistry (Fig. 5), Western blot, and qRT-PCR. Grade III and grade IV gliomas showed a pronounced decrease in miR-106a levels compared with grade I and II gliomas (Fig. 1a). In contrast, a marked increase in the protein expression of E2F1 was observed in grade III and IV gliomas compared with grade I and II gliomas (Fig. 5a, b). Therefore, low expression ...
Context 2
... WHO grades by immunohistochemistry (Fig. 5), Western blot, and qRT-PCR. Grade III and grade IV gliomas showed a pronounced decrease in miR-106a levels compared with grade I and II gliomas (Fig. 1a). In contrast, a marked increase in the protein expression of E2F1 was observed in grade III and IV gliomas compared with grade I and II gliomas (Fig. 5a, b). Therefore, low expression of miR- 106a in human glioma specimens was significantly corre- lated with high levels of E2F1 protein and high WHO grade. In addition, the levels of nuclear E2F1 protein were higher in glioma tissues than those in NATs, as determined by immunohistochemistry. However, E2F1 mRNA expres- sion was unchanged in ...
Citations
... MicroRNAs (miRNA) are non-coding RNAs (ncRNAs) that are widely found in eukaryotes and are ∼22 nucleotides in length (Takahashi et al., 2009;Su et al., 2014;Michailidi et al., 2015). Regulates cellular functions, including migration and invasion, by binding to target mRNAs (Yang et al., 2011;Bovell et al., 2013;Kumar et al., 2013;Yin et al., 2015). Several studies have shown that alterations in miRNA expression can regulate apoptosis, proliferation, tumorigenesis, invasion, and migration, and can also be involved in the occurrence, development, and recurrence of gliomas (Godlewski et al., 2008;Lin et al., 2013;Singh et al., 2013;Yeh et al., 2013;. ...
Gliomas are the most common primary malignant brain tumors and are highly aggressive. Invasion and migration are the main causes of poor prognosis and treatment resistance in gliomas. As migration and invasion occur, patient survival and prognosis decline dramatically. MicroRNAs (miRNAs) are small, non-coding 21–23 nucleotides involved in regulating the malignant phenotype of gliomas, including migration and invasion. Numerous studies have demonstrated the mechanism and function of some miRNAs in glioma migration and invasion. However, the biological and clinical significance (including diagnosis, prognosis, and targeted therapy) of glioma migration and invasion-related miRNAs have not been systematically discussed. This paper reviews the progress of miRNAs-mediated migration and invasion studies in glioma and discusses the clinical value of migration and invasion-related miRNAs as potential biomarkers or targeted therapies for glioma. In addition, these findings are expected to translate into future directions and challenges for clinical applications. Although many biomarkers and their biological roles in glioma invasion and migration have been identified, none have been specific so far, and further exploration of clinical treatment is still in progress; therefore, we aimed to further identify specific markers that may guide clinical treatment and improve the quality of patient survival.
... The role of MiR-106a in the development of tumor malignancy is complex and controversial. Several studies have shown that MiR-106a can act as a tumor suppressor or oncogene in various cancer types, depending on the cellular context (Yang et al., 2011;Kim et al., 2012). In this study, we focused on MiR-106a, which is located on chromosome X and has received little attention in BC despite the strong correlation between sex and the incidence of BC well as its correlation with RAF-1 levels (Li et al., 2018). ...
Objective:
MicroRNAs (MiRNAs) regulate mammalian cell growth, differentiation, and apoptosis by altering the expression of other genes and serve multiple roles in tumorigenesis and progression. Proto-oncogene serine/threonine-protein kinase (RAF-1) functions as a part of the MAPK/ERK signal transduction pathway. The present study aim was to prospectively evaluate MicroRNA 106a (MiR-106a) and RAF-1 as a diagnostic and prognostic factor in early prediction of breast cancer (BC), recurrence and early detection of distant metastasis as well as to analyses the statistical correlation between MiR-106a and RAF-1 levels and clinical-pathological parameters including tumor size, lymph node, histological type and grading.
Methods:
Sera and plasma of 30 normal women and 50 women with breast carcinoma were assayed for MiR-106a by RT-qPCR as well as levels of Hb, WBCs and platelets count and RAF-1 by solid phase enzyme-linked immunosorbent assay (ELISA).
Results:
The patients' characteristics, they were classified according to grade into 8% grade I, 66% grade II, 22% grade III and 4% grade IV. The stages were classified according to the TNM system as stage II was the highest percentage 66%, while the lowest percentage was 10% for stage I and 24% for stage III. Also, Hb% and RAF-1 levels were significantly decreased in breast cancer patients as compared with healthy control. On the other hand, MiRNA-106a gene expression was non-significantly increased in positive lymph node metastasis patients (FC=3.66) when compared to patients with negative lymph node metastasis (FC=3.51). In addition, MiR-106a was significantly up-regulated in breast cancer patients with a fold of change 3.63 when compared to control samples.
Conclusion:
Expression of MiR-106a gene can be used as a diagnostic and prognostic noninvasive biomarker which can stimulates breast cancer cell invasion and proliferation through downregulation of Raf-1 levels.
.
... In human gastric cancer cells, E2F1 silencing led to increased apoptosis rates [Xie et al., 2009;Wang et al., 2011], but there is no information about cell death induction in GBM cells under condition of E2F1 suppression. Interestingly, apoptosis was detected after E2F1 targeting through miRNA (miR-106a) expres-sion in glioma cells [Yang et al., 2011]. The reduction of cell proliferation could also be due to the decreased cyclin A expression, a known E2F1 target, as observed in E2F1 silenced rat glioma cells [Dos Reis Vasques et al., 2010]. ...
Glioblastoma (GBM) is an aggressive malignant brain tumor; surgery, radiation, and temozolomide still remain the main treatments. There is evidence that E2F1 is overexpressed in various types of cancer, including GBM. E2F1 is a transcription factor that controls the cell cycle progression and regulates DNA damage responses and the proliferation of pluripotent and neural stem cells. To test the potentiality of E2F1 as molecular target for GBM treatment, we suppressed the E2F1 gene (siRNA) in the U87MG cell line, aiming to inhibit cellular proliferation and modulate the radioresistance of these cells. Following E2F1 suppression, associated or not with gamma-irradiation, several assays (cell proliferation, cell cycle analysis, neurosphere counting, and protein expression) were performed in U87MG cells grown as monolayer or neurospheres. We found that siE2F1-suppressed cells showed reduced cell proliferation and increased cell death (sub-G1 fraction) in monolayer cultures, and also a significant reduction in the number of neurospheres. In addition, in irradiated cells, E2F1 suppression caused similar effects, with reduction of the number of neurospheres and neurosphere cell numbers relative to controls; these results suggest that E2F1 plays a role in the maintenance of GBM stem cells, and our results obtained in neurospheres are relevant within the context of radiation resistance. Furthermore, E2F1 suppression inhibited or delayed GBM cell differentiation by maintaining a reasonable proportion of CD133+ cells when grown at differentiation condition. Therefore, E2F1 proved to be an interesting molecular target for therapeutic intervention in U87MG cells.
... ACER2 is one of the human alkaline ceramidases, and can produce lncRNA lnc-ACER2-1. MiRNA hsa-miR-106a-5p can participate in various biological processes, and are involved in severe diseases (e.g., gastric carcinoma and glioblastoma) [37,38]. Some researchers have discovered that the expression of hsa-miR-106a-5p is down-regulated in breast tissues, and ACER2 could serve as a target gene of hsa-miR-106a-5p [39]. ...
Background
Researchers discover LncRNA–miRNA regulatory paradigms modulate gene expression patterns and drive major cellular processes. Identification of lncRNA-miRNA interactions (LMIs) is critical to reveal the mechanism of biological processes and complicated diseases. Because conventional wet experiments are time-consuming, labor-intensive and costly, a few computational methods have been proposed to expedite the identification of lncRNA-miRNA interactions. However, little attention has been paid to fully exploit the structural and topological information of the lncRNA-miRNA interaction network.
Results
In this paper, we propose novel lncRNA-miRNA prediction methods by using graph embedding and ensemble learning. First, we calculate lncRNA-lncRNA sequence similarity and miRNA-miRNA sequence similarity, and then we combine them with the known lncRNA-miRNA interactions to construct a heterogeneous network. Second, we adopt several graph embedding methods to learn embedded representations of lncRNAs and miRNAs from the heterogeneous network, and construct the ensemble models using two ensemble strategies. For the former, we consider individual graph embedding based models as base predictors and integrate their predictions, and develop a method, named GEEL-PI. For the latter, we construct a deep attention neural network (DANN) to integrate various graph embeddings, and present an ensemble method, named GEEL-FI. The experimental results demonstrate both GEEL-PI and GEEL-FI outperform other state-of-the-art methods. The effectiveness of two ensemble strategies is validated by further experiments. Moreover, the case studies show that GEEL-PI and GEEL-FI can find novel lncRNA-miRNA associations.
Conclusion
The study reveals that graph embedding and ensemble learning based method is efficient for integrating heterogeneous information derived from lncRNA-miRNA interaction network and can achieve better performance on LMI prediction task. In conclusion, GEEL-PI and GEEL-FI are promising for lncRNA-miRNA interaction prediction.
... MiR-106a belongs to the miR-17 family [29]. Studies had shown that miR-106a was highly expressed and exerted promoting role in GC [30], prostate carcinoma [31] and other carcinomas while it was down-regulated and exerted inhibiting role in glioma [32], renal cell carcinoma [33] and other carcinomas. In addition, miR-106a also participated in carcinoma diagnosis and prognosis assessment. ...
Background:
Gastric carcinoma (GC) is a common malignant tumor. Recently, it has been found that long non-coding RNAs (lncRNAs) play important role in cancer. In this paper, we investigated the effects and mechanism of lncRNA GASL1 in GC cells.
Methods:
GASL1 level in GC cells was up-regulated via cell transfection. Cell proliferation, migration, invasion were detected by CCK-8, BrdU, Transwell assays and western blot. In addition, the regulation of GASL1 on microRNA (miR)-106a level was detected using RT-qPCR and the binding between GASL1 and miR-106a was confirmed by bioinformatic prediction and luciferase reporter assay. The effects of overexpressing miR-106a on GASL1-regulated GC cell behaviors were further explored. Moreover, western blot also was used to detect the pathway-related proteins.
Results:
Overexpression of GASL1 decreased the viability and BrdU levels. Meanwhile, CyclinD1 level was decreased while p53 and p21 levels were strengthened by overexpression of GASL1. On cell metastasis, up-regulation of GASL1 decreased cell migration, invasion and related proteins matrix metalloproteinase (MMP)-9 and Vimentin levels. Meanwhile, silencing GASL1 exerted opposite effects on GC cells. Moreover, GASL1 negatively regulated and targeted miR-106a. Up-regulation of miR-106a weakened the functions of GASL1 in cell proliferation and metastasis. Besides, GASL1 decreased the relate-protein levels of PI3K/AKT and ras/raf/MEK/ERK pathways while miR-106a weakened these changes.
Conclusion:
GASL1 restrained GC cell proliferation and metastasis and blocked PI3K/AKT and ras/raf/MEK/ERK pathways by sponging miR-106a.
... Previous researches revealed that miR-106a was abnormally expressed in different types of carcinoma, functioning as a tumor suppressor or an oncogene. Of note, miR-106a induces apoptosis of glioma cells independent of p53 status and inhibits cell proliferation and glucose uptake by targeting various downstream molecules 17,18 . In non-small cell lung cancer (NSCLC) miR-106a could also inhibit cell growth 19 . ...
Objective:
Abdominal aortic aneurysm (AAA) rupture is a dramatic and lethal clinical condition with a high risk of death. Emerging evidence indicates a role for miRNAs in AAA pathogenesis, therefore we aimed to identify miRNAs that differently expressed in exosomes from AAA patients and explore the underlying mechanisms of how miR-106a plays its role in this disease.
Patients and methods:
Exosomes were isolated from plasma of AAA patients, as well as from the tissue-conditioned culture medium. The exosomal expression profiles of several miRNAs including miR-106a were analyzed by quantitative RT-PCR. To determine the potential role of miR-106a in the pathogenesis of AAA, miR-106a was overexpressed in vascular smooth muscle cells (VSMCs), and then cell viability and apoptosis were evaluated by performing CCK-8 assay and flow cytometry, respectively. Afterwards, enzyme-linked immunosorbent assay (ELISA) was applied to assess the expression levels of some proteins involved in the modulation of extracellular matrix (ECM) homeostasis. Furthermore, the target gene of miR-106a was predicted and verified through Dual-Luciferase reporter assay.
Results:
MiR-106a was up-regulated in exosomes from plasma of those patients with AAA as compared with healthy peers. Likely, increased level of miR-106a was observed in exosomes released from AAA tissue in comparison to those from adjacent normal tissues. Enhanced expression of miR-106a in VSMCs suppressed cell viability but promoted cellular apoptosis, whereas inhibition of miR-106a in VSMCs resulted in a significant decrease in the percentage of apoptotic cells compared to the control group. In addition, the protein levels of matrix metalloproteinases (MMPs, including MMP-2 and MMP-12) secreted from VSMCs were significantly up-regulated, while their inhibitor TIMP-2 was down-regulated due to miR-106a overexpression. Finally, TIMP-2 was validated subsequently as the direct target of miR-106a through Dual-Luciferase reporter assay.
Conclusions:
In aggregate, our results suggest that increased expression of miR-106a promotes VSMC cell apoptosis and down-regulates TIMP-2 through directly targeting its 3'-UTR, which in turn restores MMP production and ultimately accelerates ECM degradation. Therefore miR-106a is proposed to play a crucial role in AAA development and this will provide an update on the understanding of the clinical value of miRNAs as novel therapeutic targets for the treatment of this disease.
... MIR106A-5p, cytogenetically located on Xq26.2, acts as oncogene and tumor suppressor in different cancers [18,19]. However, the regulatory mechanism underlying the oncogenic effects of MIR106A-5p has not been elucidated. ...
Dysregulated microRNAs (miRNAs) are involved in carcinoma progression, metastasis, and poor prognosis. We demonstrated that in nasopharyngeal carcinoma (NPC), transactivated MIR106A-5p promotes a malignant phenotype by functioning as a macroautophagy/autophagy suppressor by targeting BTG3 (BTG anti-proliferation factor 3) and activating autophagy-regulating MAPK signaling. MIR106A-5p expression was markedly increased in NPC cases based on quantitative real-time PCR, miRNA microarray, and TCGA database analysis findings. Moreover, MIR106A-5p was correlated with advanced stage, recurrence, and poor clinical outcomes in NPC patients. In addition to three-dimensional cell culture assays, zebrafish and BALB/c mouse tumor models revealed that overexpressed MIR106A-5p targeted BTG3 and accelerated the NPC malignant phenotype by inhibiting autophagy. BTG3 promoted autophagy, and its expression was correlated with poor prognosis in NPC. Attenuation of autophagy, mediated by the MIR106A-5p-BTG3 axis, occurred because of MAPK pathway activation. MIR106A-5p overexpression in NPC was due to increased transactivation by EGR1 and SOX9. Our findings may lead to novel insights into the pathogenesis of NPC.
Abbreviations
ACTB: actin beta; ATG: autophagy-related; ATG5: autophagy related 5; BLI: bioluminescence; BTG3: BTG anti-proliferation factor 3; CASP3: caspase 3; ChIP: chromatin immunoprecipitation; CQ: chloroquine; Ct: threshold cycle; DAPI: 4ʹ,6-diamidino-2-phenylindole; DiL: 1,1ʹ-dioctadecyl-3,3,3ʹ,3ʹ-tetramethylindocarbocyanine perchlorate; EBSS: Earle’s balanced salt solution; EGR1: early growth response 1; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GEO: Gene Expression Omnibus; GFP: green fluorescent protein; IF: immunofluorescence; IHC: immunohistochemistry; ISH: in situ hybridization; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; MIR106A-5p: microRNA 106a-5p; miRNAs: microRNAs; MKI67: marker of proliferation ki-67; mRNA: messenger RNA; MTOR: mechanistic target of rapamycin kinase; NPC: nasopharyngeal carcinoma; qRT-PCR: quantitative real-time PCR; siRNA: small interfering RNA; SOX9: SRY-box transcription factor 9; SQSTM1: sequestosome 1; TCGA: The Cancer Genome Atlas; WB: western blot.
... MiR-106a-5p is highly expressed in gastric [38][39][40][41][42], breast [43,44], colorectal [45], and non-small cell lung cancers [46]. In squamous cell carcinomas [47], colon cancers [48], and gliomas [49], miR-106a-5p is expressed at relatively low levels. Studies have also shown that in colorectal cancer, the inhibition of the anti-metastatic gene transforming growth factor-b receptor 2 (TGFBR2) increases cell migration and invasion via miR-106a-5p [45]. ...
Background:
Immune escape is an immunological mechanism underlying tumorigenesis, and T cells play an important role in this process. In this study, immune-related genes were evaluated in tumor-infiltrating CD4+ and CD8+ T cells in colon cancer.
Methods:
ESTIMATE was used to calculate stromal and immune scores for tumor datasets downloaded from The Cancer Genome Atlas-Colon Cancer (COAD). Differentially expressed genes (DEGs) between samples with high and low stromal and immune scores were screened, followed by a functional enrichment analysis of the overlapping DEGs. The DEGs related to CD4+ and the CD8+ T cells were then screened. Predicted miRNA-mRNA and lncRNA-miRNA pairs were used to construct a competing endogenous RNA (ceRNA) network. Furthermore, chemical-gene interactions were predicted for genes in the ceRNA network. Kaplan-Meier survival curves were also plotted.
Results:
In total, 83 stromal-related DEGs (5 up-regulated and 78 down-regulated) and 1270 immune-related DEGs (807 up-regulated and 293 down-regulated genes) were detected. The 79 overlapping DEGs were enriched for 39 biological process terms. Furthermore, 79 CD4+ T cell-related genes and 8 CD8+ T cell-related genes, such as ELK3, were screened. Additionally, ADAD1 and DLG3, related to CD4+ T cells, were significantly associated with the prognosis of patients with colon cancer. The chr22-38_28785274-29,006,793.1-miR-106a-5p-DDHD1 and chr22-38_28785274-29,006,793.1-miR-4319-GRHL1 axes obtained from CD4+ and CD8+ T cell-related ceRNAs were identified as candidates for further studies.
Conclusion:
ELK3 is a candidate immune-related gene in colon cancer. The chr22-38_28785274-29,006,793.1-miR-106a-5p-DDHD1 and chr22-38_28785274-29,006,793.1-miR-4319-GRHL1 axes may be related to CD4+ and CD8+ T cell infiltration in colon cancer.
... Aberrant presence of miR-106a was positively correlated with poor prognosis, enhanced capability of invasive growth and metastasis in gastric and ovarian cancer, conversely, dysregulated miR-106a was an independent predictor for poor survival in breast cancer, osteosarcoma, glioblastoma and astrocytoma (4,(35)(36)(37)(38)(39)(40)(41). Several genes correlated with the regulation of miR-106a were proposed on tumor development, progression and drug resistance (6,36,39,41,42). ...
... Moreover, the migration and invasion abilities were also suppressed by upregulated miR-106a. In line with our study, previous studies found that enforced expression of miR-106a could inhibit cell proliferation and induce cell apoptosis via targeting E2F1 or FASTK in nervous system neoplasms (42,44). Taken together, our findings indicated that overexpression of miR-106a exerted tumor suppression effects through inducing apoptosis and inhibiting proliferation, migration, and invasion by targeting IL-8 in PCa. ...
Background:
Tumor-derived interleukin-8 (IL-8) promotes tumorigenesis and progression of prostate cancer (PCa). MicroRNAs (miRNAs) are noncoding regulatory RNAs and their dysregulation is known to be implicated in carcinogenesis. However, the post-transcriptional mechanism of IL-8 via miRNAs is not fully understood. This study was intended to investigate whether miR-106a could affect the progression of PCa via targeting IL-8 or not.
Methods:
Using bioinformatics analysis, we postulated that IL-8 might be post-transcriptionally regulated by miR-106a. This was validated by dual reporter gene assays that miR-106a could bind to the predicted site of IL-8 mRNA. To determine the biological effects of miR-106a on PCa cells (PC-3 and DU145), MTT, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), migration and invasion assays were performed.
Results:
We found that miR-106a was barely expressed in PCa cells, whereas IL-8 was aberrantly upregulated. Elevated miR-106a could reduce IL-8 expression by directly binding the 3'-UTR of IL-8. Overexpression of miR-106a in PCa cells triggered cell apoptosis and suppressed cell proliferation, migration, and invasion.
Conclusions:
This research showed that miR-106a could function as a tumor-suppressor by decreasing IL-8 levels in PCa.
... miR-106a has also been found to be overexpressed in gastric, colorectal, colorectal and pancreatic cancer tissues, but downregulated in glioma in which it was shown to have an anticancer role (21,25). However, high tissue levels of miR-106a have been reported to be associated with glioma invasion through the targeting of metalloproteinase-2, 3 and 4 (26). ...
Cholangiocarcinoma (CCA) is a malignant tumour originating from biliary epithelial cells, and is increasing in incidence. Radical surgery is the main treatment. However, the pathogenesis of CCA is unclear. Noncoding RNAs (ncRNAs) are non‑protein‑coding RNAs produced by genomic transcription that include microRNAs (miRNAs), circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs). They play important roles in gene expression, epigenetic modification, cell proliferation, differentiation and reproduction. ncRNAs also serve key roles in cancer development. Numerous studies have been carried out on ncRNAs, and associated publications have shown that ncRNAs are closely associated with the physiological and pathological mechanisms of CCA. The findings of these studies can provide new insights into the diagnosis, treatment and prognosis of CCA. The present review summarizes the pathophysiological mechanisms of different types of ncRNAs, including miRNAs, circRNAs and lncRNAs in CCA, and their applications in the diagnosis and treatment of CCA.
