MicroRNA‐10b regulates tumorigenesis in neurofibromatosis type 1

Chai, Guolin; Liu, Ning; Ma, Junrong; Li, Hua; Oblinger, Janet L.; Prahalad, Agasanur K.; Gong, Meng; Chang, Long-Sheng; Wallace, Margaret R.; Muir, David; Guha, Abhijit; Phipps, Roger J.; Hock, Janet M.; Yu, Xijie

doi:10.1111/j.1349-7006.2010.01616.x

Cited by 96 publications

(80 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It has been reported that miR-10b was upregulated in all glioma samples compared with nonneoplastic brain tissues; the expression level of miR-10b was associated with higher-grade glioma and the tumor invasive factors uPAR and RhoC [9]. Moreover, the overexpression level of miR-10b was observed in many other cancers, including neurofibromatosis type 1, esophageal cancer, pancreatic cancer, nasopharyngeal carcinoma, hepatocellular carcinoma, and colorectal cancer [11][12][13][14][15][16]. These findings suggested that miR-10b was strongly expressed in highly metastatic cancer cells and played a central role in cancer metastasis.…”

Section: Introductionmentioning

confidence: 93%

DNA methylation downregulated mir-10b acts as a tumor suppressor in gastric cancer

et al. 2014

View full text Add to dashboard Cite

Background MicroRNAs act as tumor suppressors or oncogenes. The pathological roles of miRNAs in gastric tumorigenesis are largely unknown. Although miR-10b was identified as an miRNA deregulator expressed in gastric cancer (GC), there also exists some debate on whether miR-10b is acting as tumor suppressor or oncogene in GC. Methods Quantitative RT-PCR was employed to investigate the level of miR-10b in GC tissues and matched adjacent normal tissues (n = 100). In vitro cell proliferation, apoptosis assays, cell migration, and invasion assays were performed to elucidate the biological effects of miR10b. Because silencing of miRNA by promoter CpG island methylation may be an important mechanism in tumorigenesis, GC cells were treated with 5-aza-2 0 -deoxycytidine and trichostatin A, and expression changes of miR-10b were subsequently examined by quantitative RT-PCR. Furthermore, the methylation status of the CpG island upstream of miR-10b was analyzed by methylation-specific PCR in GC tissues (n = 29). Results We showed here that miR-10b was significantly downregulated in GC cell lines and tissues as demonstrated by quantitative real-time PCR. Overexpression of miR-10b in MGC-803 and HGC-27 dramatically suppressed cell proliferation, migration, invasion, and induced apoptosis. Moreover, we demonstrated that T-cell lymphoma invasion and metastasis (Tiam1) was a target of miR-10b. Furthermore, 5-aza-2 0 -deoxycytidine and trichostain A increased miR-10b expression, and the methylation level was high in the CpG islands upstream of miR-10b gene. Conclusions Taken together, these findings suggest that miR-10b may function as a novel tumor suppressor and is partially silenced by DNA hypermethylation in GC.

show abstract

Section: Introductionmentioning

confidence: 93%

DNA methylation downregulated mir-10b acts as a tumor suppressor in gastric cancer

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Function of miR-10b has mainly been studied in breast cancer. In vitro it has been shown to promote migration and invasion in breast and esophageal cancer cell lines, as well as malignant peripheral nerve sheath tumor cell lines (51,57,58). In vivo studies also highlight the importance of miR-10b in metastasis, since mice treated systemically with antagomiR-10b developed less metastasis than their non-treated counterparts (59).…”

Section: Discussionmentioning

confidence: 99%

miRNAs can predict prostate cancer biochemical relapse and are involved in tumor progression

Fendler

Jung²,

Stephan³

et al. 2011

Int J Oncol

View full text Add to dashboard Cite

Abstract. Prostate cancer is the leading cancer diagnosed and the second most common cause of cancer related death in the western world. For prognostic monitoring after prostatectomy, recurrent increase of prostate-specific antigen (PSA), the so-called PSA or biochemical relapse remains the leading biomarker. There is currently no biomarker that can accurately predict the risk of relapse at the time of surgery. We analyzed formalin-fixed and paraffin-embedded tissue samples from 52 primary prostate cancers and normal adjacent tissues obtained after radical prostatectomy. Patients were grouped into two categories: i) patients with early biochemical relapse (<1 year after radical prostatectomy) and ii) patients with late or no biochemical relapse (>2 years after surgery). Multiplex real-time quantitative polymerase chain reaction (RT-qPCR) analysis was performed to identify a miRNA signature that can predict relapse. Results were validated by quantitative RT-PCR analysis. We identified 63 miRNAs that were differentially expressed among the same categories of patients, of whom 35 miRNAs were up-regulated and 28 were down-regulated. Literature search shows that many of these miRNAs have an established prognostic significance in other cancers and can be actively involved in tumor progression. Target prediction analysis showed that predicted targets of these miRNAs could be involved in biological processes and pathways that enhance tumor progression. We experimentally validated the role of one of the dysregulated miRNAs (miR-10b) in relapse using proliferation and wound-healing assay. miRNAs can be reliable predictive markers for biochemical relapse of prostate cancer at the time of radical prostatectomy. This should have significant impact on patient managing plans.

show abstract

“…53,59 A recent study has shown that a microRNA, miR-10b, may regulate NF1 tumorigenesis by targeting the NF1 mRNA 3= untranslated region and modulating the Ras signaling pathway. 64 In general, microRNAs hybridize to the 3= untranslated region of target mRNAs and can repress mRNA translation or mediate its cleavage.…”

Section: Regulation Of Nf1 Gene Expressionmentioning

confidence: 99%

The Pathoetiology of Neurofibromatosis 1

Jouhilahti

Peltonen

Heape

et al. 2011

The American Journal of Pathology

158

150

View full text Add to dashboard Cite

Although a mutation in the NF1 gene is the only factor required to initiate the neurocutaneous-skeletal neurofibromatosis 1 (NF1) syndrome, the pathoetiology of the multiple manifestations of this disease in different organ systems seems increasingly complex. The wide spectrum of different clinical phenotypes and their development, severity, and prognosis seem to result from the cross talk between numerous cell types, cell signaling networks, and cell-extracellular matrix interactions. The bi-allelic inactivation of the NF1 gene through a "second hit" seems to be of crucial importance to the development of certain manifestations, such as neurofibromas, café-au-lait macules, and glomus tumors. In each case, the second hit involves only one cell type, which is subsequently clonally expanded in a discrete lesion. Neurofibromas, which are emphasized in this review, and cutaneous neurofibromas in particular, are known to contain a subpopulation of NF1-diploinsufficient Schwann cells and a variety of NF1-haploinsufficient cell types. A recent study identified a multipotent precursor cell population with an NF1 ؉/؊ genotype that resides in human cutaneous neurofibromas and that has been suggested to play a role in their pathogenesis. café-au-lait macules and multiple benign cutaneous neurofibromas, which, typically, are detectable in adulthood by simple visual inspection.NF1 can affect nearly every organ system, and the complications vary between individuals, even within a single family. The clinical diagnosis is based on the presence of two or more of the following findings: six or more café-au-lait macules with diameters Ͼ5 mm in prepubertal patients and Ͼ15 mm in postpubertal patients; two or more neurofibromas of any type or one plexiform neurofibroma; axillary or inguinal freckling; optic glioma; two or more Lisch nodules of the iris; a distinctive osseous lesion, such as sphenoid wing dysplasia or pseudarthrosis; or a first-degree relative diagnosed as having NF1 according to the preceding criteria. 3 It has been suggested that a pathogenic mutation in the NF1 gene be added to the list of diagnostic criteria. 4 The most common complications of NF1 are included in the previously listed diagnostic criteria. Additional features include short stature, scoliosis, headache, speech disorders, attention deficit disorder and attention-deficit/ hyperactivity disorder, and learning disabilities. Rare complications, affecting Ͻ5% of patients, include epilepsy, hydrocephalus, cardiovascular problems, and dystrophic scoliosis. 5 The lifetime risk of malignant tumors arising from peripheral nerves is estimated to be 10% to 13%. 6 The pathoetiology of the complications in NF1 is, however, largely unknown. Genetic BackgroundNF1 is caused by mutations in the NF1 gene that encodes the tumor suppressor protein neurofibromin. 7,8 The NF1 gene is located on chromosome band 17q11.2, spanning approximately 280 kb of genomic DNA, and is composed of 57 constitutive exons and 4 alternatively spliced exons (9a, 10a2, 23a, and 48a). 9 Howeve...

show abstract

MicroRNA‐10b regulates tumorigenesis in neurofibromatosis type 1

Cited by 96 publications

References 44 publications

DNA methylation downregulated mir-10b acts as a tumor suppressor in gastric cancer

DNA methylation downregulated mir-10b acts as a tumor suppressor in gastric cancer

miRNAs can predict prostate cancer biochemical relapse and are involved in tumor progression

The Pathoetiology of Neurofibromatosis 1

Contact Info

Product

Resources

About