Dysregulated microRNAs affect pathways and targets of biologic relevance in nasal-type natural killer/T-cell lymphoma

Ng, Siok-Bian; Yan, Junli; Huang, Gaofeng; Selvarajan, V.; Tay, Jim Liang-Seah; Lin, Bin; Bi, Chonglei; Tan, Joy; Kwong, Yok–Lam; Shimizu, Norio; Aozasa, Katsuyuki; Chng, Wee‐Joo

doi:10.1182/blood-2011-07-364224

Cited by 99 publications

(120 citation statements)

References 32 publications

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“…The proliferation impairment and the loss of clonogenic potential that we observed in BL upon miR-28 reexpression are consistent with previous observations in colorectal cancer and in nasal-type natural killer/T-cell lymphoma, in which several miRNAs, including miR-28, have been reported to affect proliferation (14,16). Nonetheless, the mechanisms and the genes that are involved in these phenotypes remained unknown.…”

Section: Mir-28 As a Candidate Tumor Suppressor In Gc-derived Lymphomassupporting

confidence: 80%

“…These apparently inconsistent observations are not surprising because it is well established that miRNAs can act both as tumor suppressors and oncogenes depending on the cell context (29). Analogously to colorectal cancer and nasal-type natural killer/T-cell lymphoma (14,16), we found that miR-28 is significantly down-regulated in the majority of B-NHL and appears to be consistently silenced in all BLs. In addition, the notion that miR-28 may act as a tumor suppressor is greatly supported by the Cell counts (average ± SD) are from two independent experiments each including two bulk populations and performed in triplicates.…”

Section: Mir-28 As a Candidate Tumor Suppressor In Gc-derived Lymphomasmentioning

confidence: 62%

“…Deregulated miR-28 expression has been observed in several types of cancer, including up-regulation in esophageal, cervical, and renal cancer, and in myeloproliferative malignancies and down-regulation in colorectal cancer and nasal-type natural killer/T-cell lymphoma (10)(11)(12)(13)(14)(15)(16). These apparently inconsistent observations are not surprising because it is well established that miRNAs can act both as tumor suppressors and oncogenes depending on the cell context (29).…”

Section: Mir-28 As a Candidate Tumor Suppressor In Gc-derived Lymphomasmentioning

confidence: 87%

“…Although increased levels of miR-28 expression have been observed in esophageal, cervical, renal cancer, as well as in the platelets of a fraction of myeloproliferative neoplasm patients (10)(11)(12)(13), miR-28 is down-regulated in colorectal cancer cells and nasal-type natural killer/T-cell lymphoma. In both these latter cell types, reexpression of miR-28 leads to reduced proliferation in cell lines (14)(15)(16).…”

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confidence: 99%

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microRNA 28 controls cell proliferation and is down-regulated in B-cell lymphomas

Schneider

Setty

Holmes

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Burkitt lymphoma (BL) is a highly aggressive B-cell non-Hodgkin lymphoma (B-NHL), which originates from germinal center (GC) B cells and harbors translocations deregulating v-myc avian myelocytomatosis viral oncogene homolog (MYC). A comparative analysis of microRNAs expressed in normal and malignant GC B cells identified microRNA 28 (miR-28) as significantly down-regulated in BL, as well as in other GC-derived B-NHL. We show that reexpression of miR-28 impairs cell proliferation and clonogenic properties of BL cells by modulating several targets including MAD2 mitotic arrest deficientlike 1, MAD2L1, a component of the spindle checkpoint whose downregulation is essential in mediating miR-28-induced proliferation arrest, and BCL2-associated athanogene, BAG1, an activator of the ERK pathway. We identify the oncogene MYC as a negative regulator of miR-28 expression, suggesting that its deregulation by chromosomal translocation in BL leads to miR-28 suppression. In addition, we show that miR-28 can inhibit MYC-induced transformation by directly targeting genes up-regulated by MYC. Overall, our data suggest that miR-28 acts as a tumor suppressor in BL and that its repression by MYC contributes to B-cell lymphomagenesis.

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Section: Mir-28 As a Candidate Tumor Suppressor In Gc-derived Lymphomassupporting

confidence: 80%

Section: Mir-28 As a Candidate Tumor Suppressor In Gc-derived Lymphomasmentioning

confidence: 62%

Section: Mir-28 As a Candidate Tumor Suppressor In Gc-derived Lymphomasmentioning

confidence: 87%

mentioning

confidence: 99%

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microRNA 28 controls cell proliferation and is down-regulated in B-cell lymphomas

Schneider

Setty

Holmes

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…MiRNAs play important roles in various biological processes, including development, differentiation, apoptosis, and cell proliferation (Bartel, 2004). However, very few studies have reported miRNA deregulation in BC (Yamanaka et al, 2009;Ng et al, 2011;Paik et al, 2011). Thus, the functional roles of miRNAs in BC are still not fully understood.…”

Section: Introductionmentioning

confidence: 99%

MiRNA-15a Mediates Cell Cycle Arrest and Potentiates Apoptosis in Breast Cancer Cells by Targeting Synuclein-γ

Xie²,

Chen³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Recent studies have indicated that microRNA-15a (miR-15a) is dysregulated in breast cancer (BC). We aimed to evaluate the expression of miR-15a in BC tissues and corresponding para-carcinoma tissues. We also focused on effects of miR-15a on cellular behavior of MDA-MB-231 and expression of its target gene synuclein-γ (SNCG). Materials and Methods: The expression levels of miR-15a were analysed in BC formalin fixed paraffin embedded (FFPE) tissues by microarray and quantitative real-time PCR. CCK-8 assays, cell cycle and apoptosis assays were used to explore the potential functions of miR-15a in MDA-MB-231 human BC cells. A luciferase reporter assay confirmed direct targets. Results: Downregulation of miR-15a was detected in most primary BCs. Ectopic expression of miR-15a promoted proliferation and suppressed apoptosis in vivo. Further studies indicated that miR-15a may directly interact with the 3'-untranslated region (3'-UTR) of SNCG mRNA, downregulating its mRNA and protein expression levels. SNCG expression was negatively correlated with miR-15a expression. Conclusions: MiR-15a has a critical role in mediating cell cycle arrest and promoting cell apoptosis of BC, probably by directly targeting SNCG. Thus, it may be involved in development and progression of BC.

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Downregulation of miR‐15a due to LMP1 promotes cell proliferation and predicts poor prognosis in nasal NK/T‐cell lymphoma

et al. 2013

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Nasal NK=T-cell lymphoma (NNKTL) is an Epstein-Barr virus (EBV)-associated malignancy and has distinct clinical and histological features. However, its genetic features are hitherto unclear. MicroRNAs (miRNAs) play a crucial role in the pathogenesis of several malignancies via regulating gene expression. In this study, we investigated whether the specific microRNAs were related to the tumor behaviors in NNKTL. MiRNA array and Quantitative RT-PCR analyses revealed that miR-15a was expressed at a much lower level in NNKTL cells (SNK-1, SNK-6, and SNT-8) than in normal peripheral NK cells and EBV-negative NK cell line KHYG-1. Quantitative PCR and western blot analyses showed that the expression of MYB and cyclin D1, which are validated targets of miR15a, was higher in NNKTL cells. Transfection of NNKTL cells (SNK-6 and SNT-8) with a miR-15a precursor decreased MYB and cyclin D1 levels, thereby blocking G1=S transition and cell proliferation. Knockdown of EBVencoded latent membrane protein 1 (LMP1) significantly increased miR-15a expression in SNK-6 cells. In NNKTL tissues, we found that reduced miR-15a expression, which correlated with MYB and cyclin D1 expression, was associated with poor prognosis of NNKTL patients. These data suggest that downregulation of miR-15a, possibly due to LMP1, implicates in the pathogenesis of NNKTL by inducing cell proliferation via MYB and cyclin D1. Thus, miR-15a could be a potential target for antitumor therapy and a prognostic predictor for NNKTL.

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Dysregulated microRNAs affect pathways and targets of biologic relevance in nasal-type natural killer/T-cell lymphoma

Cited by 99 publications

References 32 publications

microRNA 28 controls cell proliferation and is down-regulated in B-cell lymphomas

microRNA 28 controls cell proliferation and is down-regulated in B-cell lymphomas

MiRNA-15a Mediates Cell Cycle Arrest and Potentiates Apoptosis in Breast Cancer Cells by Targeting Synuclein-γ

Downregulation of miR‐15a due to LMP1 promotes cell proliferation and predicts poor prognosis in nasal NK/T‐cell lymphoma

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