Mantle cell lymphoma: transcriptional regulation by microRNAs

Lisio, Lorena Di; Gómez‐López, Gonzalo; Sánchez‐Beato, Margarita; Gómez-Abad, Cristina; Rodríguez, Maria E.; Villuendas, Raquel; Ferreira, Bibiana I.; Carro, Ángel; Rico, Daniel; Mollejo, Manuela; Martı́nez, Miguel Ángel; Menárguez, Javier; Díaz-Alderete, Andrea; Gil, Juana; Cigudosa, Juan C.; Pisano, David G.; Piris, Miguel Á.; Martínez, Nerea

doi:10.1038/leu.2010.91

Cited by 69 publications

(54 citation statements)

References 60 publications

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“…4 and 4C). The potential tumor suppressor role of miR-20b has been investigated wherein low circulating levels of miR-20b was reported in lung cancer and mantle cell lymphoma, also associated with poor outcome (40). Inhibition of miR-20b can lead to an increase HIF-1a and VEGF under normoxia; conversely, an increase of miR-20b in hypoxic tumor cells decreased HIF-1a and VEGF (27).…”

Section: Discussionmentioning

confidence: 99%

Potentially Prognostic miRNAs in HPV-Associated Oropharyngeal Carcinoma

Hui

Lin

et al. 2013

Clinical Cancer Research

104

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Purpose: Deregulation of miRNAs is associated with almost all human malignancies. Human papillomavirus (HPV)-associated oropharyngeal carcinoma (OPC) has a significantly more favorable outcome compared with HPV-negative OPCs; however, the underlying mechanisms are not well understood. Hence, the objectives of this study were to determine whether miRNA expression differed as a function of HPV status and to assess whether such miRNAs provide prognostic value beyond HPV status.Methods: Global miRNA profilings were conducted on 88 formalin-fixed and paraffin-embedded (FFPE) OPC biopsies (p16-positive: 56; p16-negative: 32), wherein the expression levels of 365 miRNAs plus 3 endogenous controls were simultaneously measured using quantitative real-time (qRT)-PCR. Seven FFPE specimens of histologically normal tonsils were used as controls.Results: Overall, 224 miRNAs were expressed in more than 80% of the investigated samples, with 128 (57%) being significantly differentially expressed between tumor versus normal tissues (P < 0.05). Upregulated miR-20b, miR-9, and miR-9 Ã were significantly associated with HPV/p16-status. Three miRNA sets were significantly associated with overall survival (miR-107, miR-151, miR-492; P ¼ 0.0002), diseasefree survival (miR-20b, miR-107, miR-151, miR-182, miR-361; P ¼ 0.0001), and distant metastasis (miR-151, miR-152, miR-324-5p, miR-361, miR492; P ¼ 0.0087), which retained significance even after adjusting for p16 status. The associated biologic functions of these miRNAs include immune surveillance, treatment resistance, invasion, and metastasis. Conclusion: We have identified several miRNAs, which associate with HPV status in OPC; furthermore, three candidate prognostic sets of miRNAs seem to correlate with clinical outcome, independent of p16 status. Furthermore, evaluations will offer biologic insights into the mechanisms underlying the differences between HPV-positive versus HPV-negative OPC.

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Section: Discussionmentioning

confidence: 99%

Potentially Prognostic miRNAs in HPV-Associated Oropharyngeal Carcinoma

Hui

Lin

et al. 2013

Clinical Cancer Research

104

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“…We followed the previously described procedure 21 to identify associations between differentially expressed miRNAs (FDRo0.05) and gene expression signatures (FDRo0.05). The GSEA (Pearson correlation) was used to test the enrichment of gene sets related to each corresponding miRNA.…”

Section: Mirna Target Prediction and Mirna Target Correlationmentioning

confidence: 99%

“…9,21 The relative degree of change for each miRNA was calculated using the RQ ¼ 2 À DCt method, where DCt ¼ (Ct miRNA À Ct U6 ), and with an RNU6B endogenous control. Ct values 432 were considered beyond the limit of detection.…”

Section: Quantitative Real-time Rt-pcr Analysismentioning

confidence: 99%

Splenic marginal zone lymphoma: comprehensive analysis of gene expression and miRNA profiling

et al. 2013

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Splenic marginal zone lymphoma is a small B-cell neoplasm whose molecular pathogenesis is still essentially unknown and whose differentiation from other small B-cell lymphomas is hampered by the lack of specific markers. We have analyzed the gene expression and miRNA profiles of 31 splenic marginal zone lymphoma cases. For comparison, 7 spleens with reactive lymphoid hyperplasia, 10 spleens infiltrated by chronic lymphocytic leukemia, 12 spleens with follicular lymphoma, 6 spleens infiltrated by mantle cell lymphoma and 15 lymph nodes infiltrated by nodal marginal zone lymphoma were included. The results were validated by qRT-PCR in an independent series including 77 paraffin-embedded splenic marginal zone lymphomas. The splenic marginal zone lymphoma miRNA signature had deregulated expression of 51 miRNAs. The most highly overexpressed miRNAs were miR-155, miR-21, miR-34a, miR-193b and miR-100, while the most repressed miRNAs were miR-377, miR-27b, miR-145, miR-376a and miR-424. MiRNAs located in 14q32-31 were underexpressed in splenic marginal zone lymphoma compared with reactive lymphoid tissues and other B-cell lymphomas. Finally, the gene expression data were integrated with the miRNA profile to identify functional relationships between genes and deregulated miRNAs. Our study reveals miRNAs that are deregulated in splenic marginal zone lymphoma and identifies new candidate diagnostic molecules for splenic marginal zone lymphoma.

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“…[84][85][86][87] Overexpression of members of the miR-17∼92 cluster, for example, has been associated with high MYC levels in aggressive MCL, 86 and inhibition of chemotherapyinduced apoptosis in MCL cell lines, 88 while downregulation of miR-29 has been proposed as a potential prognostic marker for this malignancy. 84 …”

Section: Mantle Cell Lymphoma (Mcl)mentioning

confidence: 99%

MicroRNAs as B-cell lymphoma biomarkers

Manterola¹,

Fernández-Mercado²,

Larrea³

et al. 2015

BLCTT

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B-cell lymphomas represent a group of more than 35 recognized mature B-cell neoplasms differentiated largely on the basis of immunohistochemical staining patterns that are often challenging to accurately diagnose. Despite having been only formally recognized just over 10 years ago, microRNAs (miRNAs) have become one of the trendiest topics in biology. Dysregulation of miRNAs is a ubiquitous feature of cancer in general, including B-cell lymphomas. Many of the miRNAs aberrantly expressed in B-cell lymphomas also play a crucial regulatory role in normal hematopoietic function. MiRNAs show great potential as novel biomarkers of cancer, as they can differentiate cancers according to diagnosis and developmental stage, even discriminating between cancers that are poorly separated histologically. Furthermore, they can be robustly measured from routinely prepared formalin-fixed paraffin-embedded biopsy material and biological fluids such as blood. Here, we consider the identity, function, and biomarker potential of miRNAs in B-cell lymphomas and, most importantly, the hurdles that remain to be overcome if they are really to become part of future clinical practice.

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Mantle cell lymphoma: transcriptional regulation by microRNAs

Cited by 69 publications

References 60 publications

Potentially Prognostic miRNAs in HPV-Associated Oropharyngeal Carcinoma

Potentially Prognostic miRNAs in HPV-Associated Oropharyngeal Carcinoma

Splenic marginal zone lymphoma: comprehensive analysis of gene expression and miRNA profiling

MicroRNAs as B-cell lymphoma biomarkers

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