TRIM8 downregulation in glioma affects cell proliferation and it is associated with patients survival

Micale, Lucia; Fusco, Carmela; Fontana, Andrea; Barbano, Raffaela; Augello, Bartolomeo; Nittis, Pasquelena De; Copetti, Massimiliano; Pellico, Maria Teresa; Mandriani, Barbara; Cocciadiferro, Dario; Parrella, Paola; Fazio, Vito Michele; Dimitri, L.; D’Angelo, Vincenzo; Novielli, Chiara; Larizza, Lidia; Daga, Antonio; Merla, Giuseppe

doi:10.1186/s12885-015-1449-9

Cited by 45 publications

(41 citation statements)

References 24 publications

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“…Human gliomas are the most common and life-threatening type of neurological malignancy in adults (22). The present study was the first, to the best of our knowledge, to investigate the role of MMP9 in glioma.…”

Section: Discussionmentioning

confidence: 84%

High expression of MMP9 in glioma affects cell proliferation and is associated with patient survival rates

et al. 2017

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Abstract. Human gliomas are a heterogeneous group of primary malignant brain tumors, which most commonly occur in the central nervous system of children and adults. Previous studies have suggested a prognostic role of matrix metalloproteinase 9 (MMP9) in glioma, however, the frequency and significance of the protein expression of MMP9 in glioma remain to be fully elucidated. In the present study, the expression of MMP9 was detected by reverse transcription-quantitative polymerase chain reaction (qPCR), western blotting and immunohistochemical staining. MTT and colony-forming assays were used to detect the role of MMP9 in the proliferation of glioma cells. MMP9 copy numbers in glioma were examined using qPCR. The results indicated that the expression level of MMP9 was significantly increased in glioma and was associated with World Health Organization (WHO) glioma grades. The high expression of MMP9 in tissues was an independent predictor of survival rates in patients with WHO grade III tumors. The overexpression of MMP9 promoted cell growth and induced a significant increase in clonogenic potential in U87 glioblastoma cell lines. These experimental data suggested that the overexpression of MMP9 in glioblastoma cells may occur primarily through an increase in gene copy number. The results of the present study suggested that the overexpression of MMP9 may be necessary for the transition to the more aggressive phenotype typical of WHO grade III gliomas, suggesting the likely involvement of the MMP9 gene in gliomagenesis and disease progression. IntroductionHuman gliomas are a heterogeneous group of primary malignant brain tumors, which most commonly occur in the central nervous system of children and adults (1). Glioblastoma multiforme (GBM), the most aggressive form of glioma, exhibits advanced features of malignancy, including rapid tumor cell proliferation, apoptosis resistance, florid necrosis and angiogenesis (2). These tumor properties are associated with poor clinical outcome by conferring resistance to chemotherapy and radiotherapy, and by promoting neurological debilitation leading to individuals succumbing to mortality within 12-18 months of diagnosis (3).Gliomas can be categorized based on the type of glial cell, which they are most histologically similar to, the location of the tumor and the aggressiveness of the cancer cells. Tumors, which are most similar to astrocytes are specifically termed astrocytomas and can be further classified into grades I-IV based on the criteria set by the World Health Organization (WHO) (4), with higher grades corresponding to more aggressive tumors. Grade I and II astrocytomas correspond to low-grade tumors, which are predominantly non-malignant. Grade III and IV astrocytomas are high-grade, malignant tumors. Grade III astrocytomas are also known as anaplastic astrocytomas, whereas grade IV astrocytomas, commonly referred to as glioblastoma, are the most aggressive of all gliomas. GBMs are also the most common type of glioma with an annual incident rate of 3.19/100,000 in ...

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Section: Discussionmentioning

confidence: 84%

High expression of MMP9 in glioma affects cell proliferation and is associated with patient survival rates

et al. 2017

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“…Increased levels of miR-182 were previously reported in papillary thyroid carcinoma 12. However, its expression in anaplastic thyroid cancer had not been investigated.…”

Section: Resultsmentioning

confidence: 95%

“…Some miRNAs are dysregulated in ATC, including miR-618,7 miR-200,8 miR-99a,9 miR-206,10 and miR-20a 11. A recent study reported overexpression of miR-182 in papillary thyroid carcinoma compared to the levels in adjacent normal tissues 12. However, the specific role of miR-182 in anaplastic thyroid cancer and the underlying mechanisms remain to be established.…”

Section: Introductionmentioning

confidence: 99%

miR-182 promotes tumor growth and increases chemoresistance of human anaplastic thyroid cancer by targeting tripartite motif 8

Liu

Zhang

Shi

et al. 2017

OTT

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Chemotherapy is one of the most effective forms of cancer treatment and has been used in the treatment of various malignant tumors. We have gained significant insight into the mechanisms of chemoresistance but the details of the molecular mechanisms remain unclear. In the present study, we found that tripartite motif 8 (TRIM8) expression was downregulated in anaplastic thyroid cancer (ATC) tissues and cell lines. This downregulation of TRIM8 was significantly correlated with the upregulation of miR-182 in human ATC tissues. Bioinformatic analysis and luciferase reporter assays identified TRIM8 as a direct target of miR-182 in ATC. A functional assay using an MTT assay and colony formation showed that miR-182 induced cellular growth by repressing TRIM8 expression. Additionally, overexpressed miR-182 contributed to the chemoresistance of ATC cells by the repression of TRIM8 expression. In conclusion, these results demonstrate that miR-182/TRIM8 may be a therapeutic target for the treatment of chemoresistant human thyroid papillary cancer.

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“…Alterations in TRIMs are associated with diverse pathological conditions, including developmental disorders, autoimmune disease, viral infections and cancer. A number of TRIMs, such as TRIM13, TRIM8, TRIM19 and TRIM26, function as tumor suppressor proteins by regulating transcriptional activity and apoptosis in a variety of cancer types2021222324. For instance, TRIM19, also known as Promyelocytic leukemia protein (PML), has a tumor suppressor function, and cells derived from PML −/− mice are defective in inducing apoptosis by Fas, TNFα, or interferons25.…”

Section: Discussionmentioning

confidence: 99%

TRIM14 is a Putative Tumor Suppressor and Regulator of Innate Immune Response in Non-Small Cell Lung Cancer

Hai

Zhu

Wang

et al. 2017

Sci Rep

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Non-small-cell lung carcinoma (NSCLC) accounts for 85% of malignant lung tumors and is the leading cause of cancer deaths. Our group previously identified Tripartite Motif 14 (TRIM14) as a component of a prognostic multigene expression signature for NSCLC. Little is known about the function of TRIM14 protein in normal or disease states. We investigated the functional and prognostic role of TRIM14 in NSCLC using in vitro and in vivo perturbation model systems. Firstly, a pooled RNAi screen identified TRIM14 to effect cell proliferation/survival in NSCLC cells. Secondly, silencing of TRIM14 expression significantly enhanced tumor growth in NSCLC xenograft mouse models, while exogenous TRIM14 expression attenuated tumorigenesis. In addition, differences in apoptotic activity between TRIM14-deficient and control tumors suggests that TRIM14 tumor suppressor activity may depend on cell death signaling pathways. TRIM14-deficient cell lines showed both resistance to hypoxia-induced cell death and attenuation of interferon response via STAT1 signaling. Consistent with these phenotypes, multivariate analyses on published mRNA expression datasets of over 600 primary NSCLCs demonstrated that low TRIM14 mRNA levels are significantly associated with poorer prognosis in early stage NSCLC patients. Our functional data therefore establish a novel tumor suppressive role for TRIM14 in NSCLC progression.

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TRIM8 downregulation in glioma affects cell proliferation and it is associated with patients survival

Cited by 45 publications

References 24 publications

High expression of MMP9 in glioma affects cell proliferation and is associated with patient survival rates

High expression of MMP9 in glioma affects cell proliferation and is associated with patient survival rates

miR-182 promotes tumor growth and increases chemoresistance of human anaplastic thyroid cancer by targeting tripartite motif 8

TRIM14 is a Putative Tumor Suppressor and Regulator of Innate Immune Response in Non-Small Cell Lung Cancer

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TRIM8 downregulation in glioma affects cell proliferation and it is associated with patients survival

Cited by 45 publications

References 24 publications

High expression of MMP9 in glioma affects cell proliferation and is associated with patient survival rates

High expression of MMP9 in glioma affects cell proliferation and is associated with patient survival rates

miR-182 promotes tumor growth and increases chemoresistance&nbsp;of human anaplastic thyroid cancer by targeting tripartite motif 8

TRIM14 is a Putative Tumor Suppressor and Regulator of Innate Immune Response in Non-Small Cell Lung Cancer

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miR-182 promotes tumor growth and increases chemoresistance of human anaplastic thyroid cancer by targeting tripartite motif 8