MicroRNA-149 is epigenetically silenced tumor-suppressive microRNA, involved in cell proliferation and downregulation of AKT1 and cyclin D1 in human glioblastoma multiforme

Ghasemi, Asghar; Fallah, Soudabeh; Ansari, Mohammad

doi:10.1139/bcb-2015-0064

Cited by 19 publications

(18 citation statements)

References 29 publications

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“…It has been reported that miR-149-5p can inhibit cell proliferation, invasion and migration in human hepatocellular carcinoma by targeting AKT1 and further facilitating the mTOR pathway [38]. The interaction between miR-149-5p and AKT1 is also reported in colon carcinoma and glioblastoma [39, 40]. Based on the assumption that circNRIP1 plays a tumour promotor role in GC through the classic ceRNA mechanism, we tried to identify the ceRNA of circNRIP1, which should also be the downstream target gene of miR-149-5p.…”

Section: Resultsmentioning

confidence: 99%

Circular RNA circNRIP1 acts as a microRNA-149-5p sponge to promote gastric cancer progression via the AKT1/mTOR pathway

et al. 2019

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BackgroundCircRNA has emerged as a new non-coding RNA that plays crucial roles in tumour initiation and development. ‘MiRNA sponge’ is the most reported role played by circRNAs in many tumours. The AKT/mTOR axis is a classic signalling pathway in cancers that sustains energy homeostasis through energy production activities, such as the Warburg effect, and blocks catabolic activities, such as autophagy. Additionally, the AKT/mTOR axis exerts a positive effect on EMT, which promotes tumour metastasis.MethodsWe detected higher circNRIP1 expression in gastric cancer by performing RNA-seq analysis. We verified the tumour promotor role of circNRIP1 in gastric cancer cells through a series of biological function assays. We then used a pull-down assay and dual-luciferase reporter assay to identify the downstream miR-149-5p of circNRIP1. Western blot analysis and immunofluorescence assays were performed to demonstrate that the circNRIP1-miR-149-5p-AKT1/mTOR axis is responsible for the altered metabolism in GC cells and promotes GC development. We then adopted a co-culture system to trace circNRIP1 transmission via exosomal communication and RIP experiments to determine that quaking regulates circNRIP1 expression. Finally, we confirmed the tumour suppressor role of microRNA-133a-3p in vivo in PDX mouse models.ResultsWe discovered that knockdown of circNRIP1 successfully blocked proliferation, migration, invasion and the expression level of AKT1 in GC cells. MiR-149-5p inhibition phenocopied the overexpression of circNRIP1 in GC cells, and overexpression of miR-149-5p blocked the malignant behaviours of circNRIP1. Moreover, it was proven that circNRIP1 can be transmitted by exosomal communication between GC cells, and exosomal circNRIP1 promoted tumour metastasis in vivo. We also demonstrated that quaking can promote circNRIP1 transcription. In the final step, the tumour promotor role of circNRIP1 was verified in PDX models.ConclusionsWe proved that circNRIP1 sponges miR-149-5p to affect the expression level of AKT1 and eventually acts as a tumour promotor in GC.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0935-5) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Circular RNA circNRIP1 acts as a microRNA-149-5p sponge to promote gastric cancer progression via the AKT1/mTOR pathway

et al. 2019

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“…2, 25 2 It has been well established that miR-149 is epigenetically silenced in GBM, and its overexpression not only suppresses tumor cell proliferation but also increases the sensitivity of cancer cells to chemotherapy. [26][27][28][29] We, therefore, investigated the role of SLC16A1-AS1 in GBM and its potential interaction with miR-149 in this study.…”

Section: Introductionmentioning

confidence: 99%

LncRNA SLC16A1-AS1 is Upregulated in Glioblastoma and Promotes Cancer Cell Proliferation by Regulating miR-149 Methylation

Long¹,

Li²,

Jin³

et al. 2021

CMAR

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Introduction LncRNA SLC16A1-AS1 has been characterized as a critical player in lung cancer, while its role in glioblastoma (GBM) is unknown. By analyzing the TCGA dataset, we observed the upregulation of SLC16A1-AS1 expression in GBM. Therefore, we aimed to investigate the role of SLC16A1-AS1 in this cancer. Methods GBM tissues and paired non-tumor tissues were collected from 62 GBM patients through biopsy. RT-qPCR was performed to determine the expression of SLC16A1-AS1 and miR-149. Linear regression was used to analyze their correlations. The relationship between SLC16A1-AS1 and miR-149 was assessed by gain and loss of function experiments. Methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP) were performed to analyze the methylation status of miR-149. Cell proliferation was evaluated by CCK-8 assay and colony formation experiments in GBM cells. Results We found that SLC16A1-AS1 expression was upregulated in GBM tissues, and the upregulated expression of SLC16A1-AS1 predicted poor survival of GBM patients. MiR-149 was downregulated in GBM tissues and inversely correlated with the expression of SLC16A1-AS1. In GBM cells, overexpression of SLC16A1-AS1 downregulated the expression of miR-149 and increased the methylation of miR-149 gene. In cell proliferation and colony formation assay, overexpression of SLC16A1-AS1 reduced the inhibitory effects of miR-149 on GBM cell proliferation. Conclusion SLC16A1-AS1 may promote GBM cell proliferation by regulating miR-149 methylation. SLC16A1-AS1 can be considered as a potential diagnostic marker in GBM.

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“…found that 5-Aza-CdR in combination with histone deacetylase inhibitor trichostatin A (TSA) could increase miR-200c in LY2 cells. In GBM, Ghasemi et al 69 . revealed that treatment of U87MG cells with 5-Aza-CdR can reverse the hypermethylation status of miR-149 and increase its expression, thus decreasing target mRNA and protein levels.…”

Section: Resultsmentioning

confidence: 99%

In Silico Prediction of Small Molecule-miRNA Associations Based on the HeteSim Algorithm

Chen

Sun

et al. 2019

Molecular Therapy - Nucleic Acids

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Targeting microRNAs (miRNAs) with drug small molecules (SMs) is a new treatment method for many human complex diseases. Unsurprisingly, identification of potential miRNA-SM associations is helpful for pharmaceutical engineering and disease therapy in the field of medical research. In this paper, we developed a novel computational model of HeteSim-based inference for SM-miRNA Association prediction (HSSMMA) by implementing a path-based measurement method of HeteSim on a heterogeneous network combined with known miRNA-SM associations, integrated miRNA similarity, and integrated SM similarity. Through considering paths from an SM to a miRNA in the heterogeneous network, the model can capture the semantics information under each path and predict potential miRNA-SM associations based on all the considered paths. We performed global, miRNA-fixed local and SM-fixed local leave one out cross validation (LOOCV) as well as 5-fold cross validation based on the dataset of known miRNA-SM associations to evaluate the prediction performance of our approach. The results showed that HSSMMA gained the corresponding areas under the receiver operating characteristic (ROC) curve (AUCs) of 0.9913, 0.9902, 0.7989, and 0.9910 ± 0.0004 based on dataset 1 and AUCs of 0.7401, 0.8466, 0.6149, and 0.7451 ± 0.0054 based on dataset 2, respectively. In case studies, 2 of the top 10 and 13 of the top 50 predicted potential miRNA-SM associations were confirmed by published literature. We further implemented case studies to test whether HSSMMA was effective for new SMs without any known related miRNAs. The results from cross validation and case studies showed that HSSMMA could be a useful prediction tool for the identification of potential miRNA-SM associations.

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MicroRNA-149 is epigenetically silenced tumor-suppressive microRNA, involved in cell proliferation and downregulation of AKT1 and cyclin D1 in human glioblastoma multiforme

Cited by 19 publications

References 29 publications

Circular RNA circNRIP1 acts as a microRNA-149-5p sponge to promote gastric cancer progression via the AKT1/mTOR pathway

Circular RNA circNRIP1 acts as a microRNA-149-5p sponge to promote gastric cancer progression via the AKT1/mTOR pathway

LncRNA SLC16A1-AS1 is Upregulated in Glioblastoma and Promotes Cancer Cell Proliferation by Regulating miR-149 Methylation

In Silico Prediction of Small Molecule-miRNA Associations Based on the HeteSim Algorithm

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