MicroRNA-210 regulates cell proliferation and apoptosis by targeting regulator of differentiation 1 in glioblastoma cells

Zhang, Shuai; Lai, Niansheng; Liao, Keman; Sun, Junliang; Lin, Yongcheng

doi:10.5114/fn.2015.54424

Cited by 51 publications

(40 citation statements)

References 26 publications

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“…7 Like other malignant tumours, glioblastoma also exhibits abnormal cell proliferation and metastasis, which were caused by abnormal expression of a variety of genes. [8][9][10][11] C-type lectin domain family 5 member A (CLEC5A), also known as C-type lectin superfamily member 5 (CLECSF5) and myeloid DAP12associating lectin 1 (MDL1), is a C-type lectin encoded by CLEC5A gene. This gene encodes a member of C-type lectin/C-type lectinlike domain (CTL/CTLD) superfamily.…”

Section: Introductionmentioning

confidence: 99%

C‐type lectin domain family 5, member A (CLEC5A, MDL‐1) promotes brain glioblastoma tumorigenesis by regulating PI3K/Akt signalling

Fan

et al. 2019

Cell Proliferation

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Objectives: Glioblastoma is the most common malignant glioma of all brain tumours.It is difficult to treat because of its poor response to chemotherapy and radiotherapy and high recurrence rate after treatment. The aetiology of glioblastoma is a result of disorders of multiple factors. Depending on cell signal transduction, these glioblastoma-associated factors lead to cell proliferation, differentiation and apoptosis.Therefore, investigation of the potential factors which involved in the development of glioblastoma could provide a new target for the treatment of glioblastoma. Materials and methods:We analysed the transcript expression of CLEC5A in glioblastoma by accessing The Cancer Genome Atlas (TCGA). qRT-PCR was performed to detect the RNA expression of genes in cells and tissues, and Western blot was used to measure the protein levels (Cyclin D1, Bcl-2, BAX, PCNA, MMP2, MMP9, Akt and Akt phosphorylation) in tissues and cells. Cell proliferation, migration, invasion, cycle and apoptosis were measured by CCK-8, transwell and flow cytometry assays, respectively. Ki67 level and lung metastasis were determined by immunochemistry and H&E staining. Results:In this study, we found that CLEC5A was highly upregulated in glioblastoma compared to normal brain tissues, which had an opposite relation with the overall patient survival. Downregulation of CLEC5A could inhibit cell proliferation, migration and invasion via promoting apoptosis and G1 arrest. In contrast, overexpression of CLEC5A stimulated cell proliferation, migration and invasion. In addition, we found that CLEC5A level was positively correlated with Akt phosphorylation level. Akt inhibitor or agonist could reverse the modulation effects of CLEC5A in glioblastoma.Moreover, In vivo results suggested that inhibition of CLEC5A significantly reduced tumour size, weight, cell proliferation ability and lung metastasis via inhibition of phosphorylation Akt. Conclusion:Both in vitro and in vivo evidences supported that CLEC5A was involved in glioblastoma pathogenesis via regulation of PI3K/Akt pathway. Thus, CLEC5A might serve as a potential therapeutic target in the treatment of glioblastoma in the future.

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Section: Introductionmentioning

confidence: 99%

C‐type lectin domain family 5, member A (CLEC5A, MDL‐1) promotes brain glioblastoma tumorigenesis by regulating PI3K/Akt signalling

Fan

et al. 2019

Cell Proliferation

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“…One important miRNA is miR‐210, which is directly promoted by HIF1α and plays a key role in the hypoxic response. It has been reported to regulate various critical biological processes under hypoxia, such as cell cycle (He et al, ; Zuo et al, ), differentiation (Liu et al, ), apoptosis (Gou et al, ; Zhang et al, ), and mitochondrial metabolism (Chan et al, ; Chen et al, ; White et al, ), in many kinds of tumors. Moreover, clinical studies found that miR‐210 expression was significantly increased in OS tissues (Lulla et al, ).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐210 is increased and it is required for dedifferentiation of osteosarcoma cell line

Zhang

Mai

Chen

2017

Cell Biology International

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Osteosarcoma (OS) is the most common malignant bone tumor and is prevalent in adolescents. In clinical studies, miR-210 has been reported to be tightly correlated to the poor prognosis of OS. Nevertheless, its roles in OS have not been fully elucidated. In view of the central role played by OS stem cells (OSCs) in the malignant progression of OS, this study investigated the influence of miR-210 on the formation of OSCs. Our previous findings suggested that the microenvironment of bone, abundant TGF-β1 and hypoxia, could induce OS cells to dedifferentiate into OSCs. In this study, we found that miR-210 participated in the dedifferentiation of OS cells into OSCs, and inhibiting it significantly suppressed the formation of OSCs. Further results suggested that miR-210 promoted the expression of TGF-β1 and its downstream effectors Snail1 and Slug which were highly elevated in the process of OS dedifferentiation. Additionally, the target gene of miR-210 was also investigated. It was found that NFIC was significantly reduced by miR-210 treatment and also during OS dedifferentiation. Therefore, this study suggested that miR-210 promoted OS cells dedifferentiation and uncovered its role in the malignant progress of OS.

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“…It has been reported to be involved in cell survival, differentiation, angiogenesis, metabolism and cell cycle control (15,44). In addition, elevated miR-210 levels increase the proliferation and decrease apoptosis of GBM cells by targeting polypyrimidine tract binding protein 3 (45). miR-210 extracted from the peripheral blood is a promising and minimally invasive biomarker that can be employed to diagnose and predict the outcome of glioma (27).…”

Section: Discussionmentioning

confidence: 99%

Exosomal microRNA‑210 is a potentially non‑invasive biomarker for the diagnosis and prognosis of glioma

2020

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MicroRNAs (miRs) transferred by exosomes can function as non-invasive potential biomarkers for the diagnosis and prognosis in various types of cancer. The present study examined the diagnostic and prognostic value of serum exosomal-(exo-)miR-210 levels in association with hypoxic conditions in patients with glioma. Serum levels of exo-miR-210 were determined by quantitative PCR in samples obtained from patients with glioma. Patients were divided into low-and high-expression exo-miR-210 groups according to the median expression value. Statistical analyses were conducted to examine the potential value of exo-miR-210 in predicting the diagnosis and prognosis of patients with glioma. A significant increase in serum exo-miR-210 levels was observed in patients with glioma compared with healthy controls. Additionally, the expression levels of exo-miR-210 were increased with ascending pathological grades. Furthermore, expression levels of miR-210 in serum exosomes from patients with glioblastoma were markedly decreased following surgery and upregulated once more at the recurrences of primary tumors, indicating that exo-miR-210 could reflect alterations in malignant glioma loads. In addition, Kaplan-Meier analysis was performed to analyze overall survival (OS) time. Patients with malignant glioma with high exo-miR-210 expression exhibited a poorer OS compared with patients with low expression. Importantly, univariate and multivariate Cox regression analysis revealed that the expression levels of exo-miR-210 in glioma serum samples were independently associated with OS. Finally, increased serum exo-miR-210 expression was positively associated with high levels of hypoxia-inducible factor 1a and reflected hypoxia in patients with glioma. In conclusion, serum levels of exo-miR-210 may serve as a diagnostic, prognostic and hypoxic biomarker to reflect glioma status and hypoxic signatures.

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MicroRNA-210 regulates cell proliferation and apoptosis by targeting regulator of differentiation 1 in glioblastoma cells

Abstract: A b s t r a c t

Cited by 51 publications

References 26 publications

C‐type lectin domain family 5, member A (CLEC5A, MDL‐1) promotes brain glioblastoma tumorigenesis by regulating PI3K/Akt signalling

C‐type lectin domain family 5, member A (CLEC5A, MDL‐1) promotes brain glioblastoma tumorigenesis by regulating PI3K/Akt signalling

MicroRNA‐210 is increased and it is required for dedifferentiation of osteosarcoma cell line

Exosomal microRNA‑210 is a potentially non‑invasive biomarker for the diagnosis and prognosis of glioma

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