microrna profiling

Diabetes and cancer: A shared biological basis

by Christoph on September 29, 2011

in Publications

Contrary to what you might think, cancer and diabetes appear to have some biology in common. According to a report in the September 30th issue of the Cell Press journal, Cell, a pathway that initially drew attention for its role in embryonic stem cells and cancer also influences the odds that mice develop or resist diabetes.

Mice with high levels of the cancer-promoting proteins Lin28a or Lin28b become more sensitive to insulin and less prone to diabetes when on a high-fat diet, the new study shows.

“This highlights the overlap in the biology of these disorders,” said George Daley of Harvard Medical School. “It may be the same kinds of metabolic shifts that allow cancer cells to grow are also related to [whole-body] glucose metabolism.”

In fact, there were clues about such a connection, but “no obvious mechanism,” he says. For instance, studies have shown that cancer cells within a tumor are able to grow more rapidly by shifting the way they use glucose. Genome-wide association studies for type 2 diabetes have also pinpointed several susceptibility genes with known links to cancer or the cell cycle.

Daley’s team, including first authors Hau Zhu and Ng Shyh-Chang, had noticed earlier that an immature form of the microRNA (tiny bits of RNA that silence genes by targeting messenger RNA) known as let-7 is abundant in stem cells. “It allows stem cells to be stem cells,” Zhu says.

Let-7 is also important in preventing cancer, Zhu explained, and its activity is [click to continue…]

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The hippocampus is a part of the brain critically involved in memory formation and spatial navigation. Shinohara et al. (2011,) used deep sequencing for  miRNA profiling of multiple samples of the mature male rat hippocampal CA3 region. According to their study, the let-7 family miRNA represents about half of the small RNA cDNA library. Major let-7 family miRNAs are  let-7c (23%), let-7a (9%), let-7f (9%), and let-7b (7%). The authors found miR134, a miRNA previously reported to be related to synaptic plasticity and morphology, only modestly expressed (~0.05%). The miRNA profiles of the left and right hippocampi were similar.  The sequence data derived from 3 pooled data sets and each data set contained corresponding left and right hippocampal CA3 samples. This study is one of the fewest studies in which miRNA expression profiles were quantitatively assessed in a specific region of the brain. The raw sequence reads and cross-mapped results are available in the DDJB sequence archive with the accession number DRA000379 (http://trace.ddbj.nig.ac.jp/DRASearch/submission?acc=DRA000379).

miRNA profiling of bilateral rat hippocampal CA3 by deep sequencing.
Shinohara Y, Yahagi K, Kawano M, Nishiyori H, Kawazu C, Suzuki N, Manabe RI, Hirase H.
Biochem Biophys Res Commun. 2011 May 13. [Epub ahead of print]
PMID:  21575607 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21575607

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Houston, TX (PRWEB)   -  A week after the latest miRBase update LC Sciences announced use of miRBase Version 17 probe content as new default for their miRNA microarrays. Arrays for all species included in the latest miRBase 17 release are available. Looking at the most common species: while the changes in probe content for rat are negligible, additions to the list of human miRNAs are substantial: 521 new unique human mature miRNA sequences were added (see our post miRBase Version 17 Update Released).

The full press release: http://www.prweb.com/releases/2011/5/prweb8404968.htm

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Accumulating evidence suggests that microRNAs (miRNAs) are important gene regulators, which can have critical roles in diverse biological processes including tumorigenesis. In this study, researchers from Nanjing University School of Medicine analyzed the miRNA expression profiles in non-small cell lung carcinoma (NSCLC) by use of a miRNA microarray platform and identified 40 differentially expressed miRNAs.

They showed that miRNA (miR)-451 was the most downregulated in NSCLC tissues. The expression level of miR-451 was found to be significantly correlated with tumor differentiation, pathological stage and lymph-node metastasis. Moreover, low miR-451 expression level was also correlated with shorter overall survival of NSCLC patients (P<0.001). Ectopic miR-451 expression significantly suppressed the in vitro proliferation and colony formation of NSCLC cells and the development of tumors in nude mice by enhancing apoptosis, which might be associated with inactivation of Akt signaling pathway. Interestingly, ectopic miR-451 expression could significantly inhibit RAB14 protein expression and decrease a luciferase-reporter activity containing the RAB14 3′-untranslated region (UTR). In addition, RNA interference silencing of RAB14 gene could recapitulate the tumor suppressor function of miR-451, whereas restoration of RAB14 expression could partially attenuate the tumor suppressor function of miR-451 in NSCLC cells. Furthermore, they also showed that strong positive immunoreactivity of RAB14 protein was significantly associated with downregulation of miR-451 (P=0.01).

These findings suggest that miR-451 regulates survival of NSCLC cells partially through the downregulation of RAB14. Therefore, targeting with the miR-451/RAB14 interaction might serve as a novel therapeutic application to treat NSCLC patients.

Wang R, Wang ZX, Yang JS, Pan X, De W, Chen LB. (2011) MicroRNA-451 functions as a tumor suppressor in human non-small cell lung cancer by targeting ras-related protein 14 (RAB14). Oncogene [Epub ahead of print]. [abstract]

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Renal cell carcinoma (RCC) represents a spectrum of histologic subtypes that are morphologically and cytogenetically distinct. Distinguishing RCC subtypes is of clinical importance because they have different prognoses and subsequently different management plans. Attempts to distinguishing between the subtypes are usually made by morphologic assessment, which is often inconclusive and not always accurate. This can be caused by the complexity and mixed patterns of morphological features as well as simple observer variability in diagnosing subtypes among pathologists.

Researchers at the University of Toronto set out to identify microRNA signatures that can distinguish the different RCC subtypes accurately. Knowing the specific microRNA signature for each subtype provides the basis of a specific targeted therapy for the particular subtype by seeking the microRNAs.

MicroRNA microarray analysis was performed on fresh frozen tissues of three common RCC subtypes (clear cell, chromophobe, and papillary) and on oncocytoma (n=94). Results were validated on the original as well as on an independent set of tumours, using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis with microRNA-specific primers.

From the microarray data, the researchers able to develop a classification system that can distinguish the different RCC subtypes using unique microRNA signatures in a maximum of four steps. The system has a sensitivity of 97% in distinguishing normal from RCC, 100% for clear cell RCC (ccRCC) subtype, 97% for papillary RCC (pRCC) subtype, and 100% accuracy in distinguishing oncocytoma from chromophobe RCC (chRCC) subtype. This system was cross-validated and showed an accuracy of about 90%. The oncogenesis of ccRCC is more closely related to pRCC, whereas chRCC is comparable with oncocytoma. They also developed a binary classification system that can distinguish between two individual subtypes.

Youssef YM, White N, Grigull J, Krizova A, Samy C, Mejia-Guerrera S, Evans A, Youse GM. (2011) Accurate Molecular Classification of Kidney Cancer Subtypes Using MicroRNA Signature. European Urology [Epub ahead of print]. [abstract]

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Upcoming miRNA Conference: microRNA in Human Disease & Development

February 16, 2010

Monday, March 22nd – Wednesday, March 24 – 2010 in Cambridge, MA – USA miRNA as Diagnostic Biomarkers and Targets for Therapeutic Development TOPICS INCLUDE: microRNA in Cancer microRNA in Biomarker and Diagnostic Development microRNA in Therapeutic Development microRNA in Human Development and Disease microRNA Pathways and Mechanisms PRE-CONFERENCE SHORT COURSE: microRNA Identification, Profiling and […]

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MicroRNA Profiling and Head and Neck Cancer

September 25, 2009

Recent advances in microRNA expression profiling have led to a better understanding of the HNOC pathogenesis. This will lead to the identification of specific microRNA expression patterns that may become powerful biomarkers for diagnosis and prognosis of HNOC. In addition, these microRNAs may also serve as therapeutic targets for novel strategies of HNOC prevention and […]

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