breast cancer

OncomiRs coverOncomiRs is a new international, peer-reviewed, open-access journal that welcomes research relevant to the interdisciplinary nature of microRNAs and cancer biology. The journal publishes original research articles and reviews covering all the basics aspects of the microRNAs in tumor formation and development as well as their role in the treatment sensitivity and resistance. OncomiRs focuses on the basic principles of microRNAs in the regulation of cellular processes such as apoptosis, cell cycle control, metastatic dissemination, cellular senescence and immortalization. A particular attention is given to microRNA-controlled regulation of cellular oncogenes and tumor suppressor genes.

Submitting to OncomiRs gives a unique chance to highlight findings in the only specialized microRNA and cancer research journal. Moreover, due to its open access model of publication, manuscripts accepted for publication are immediately published on-line. A submission to OncomiRs also provides an opportunity to present work to our prominent Advisory Board as well as obtain advices from them.

The first article featured in OncomiRs comes from the A. Harel-Bellan’s lab from Paris Sud University in France. The paper “Mir-205 modulates acinar size and morphology of transformed breast epithelial cells” studied the function of miR-205 in cellular formation of breast cancer. Indeed normal breast epithelial cells form highly organized multi-cellular structures, the breast lobules, terminating in [click to continue…]

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MicroRNAs Suppress Cancer Metastasis

by Chris on January 26, 2011

in News

Prostate Cancer

microRNA inhibits prostate cancer metastasis by suppressing a surface protein (CD44) commonly found on prostate cancer stem cells. A research team led by scientists at The University of Texas MD Anderson Cancer Center reported in an advance online publication at Nature Medicine1.

The researchers demonstrated that miR-34a inhibits prostate cancer stem cells by suppressing CD44 and most significantly, that intravenous treatment of tumor-bearing mice with synthetic miR-34a reduced tumor burden by half in one tumor type. It also steeply reduced lung metastases in another tumor type, resulting in increased animal survival.

Breast Cancer

In a previous groundbreaking study, researchers at Memorial Sloan-Kettering Cancer Center found a specific set of microRNAs for which expression is specifically lost as human breast cancer cells develop metastatic potential2. Furthermore, they show that restoring the expression of these microRNAs in malignant cells reduces overall tumor growth and proliferation and suppresses metastatic cell invasion.

1.     Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, Patrawala L, Yan H, Jeter C, Honorio S, Wiggins JF, Bader AG, Fagin R, Brown D, Tang DG. (2011) The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med [Epub ahead of print]. [abstract]

2.     Tavazoie SF, Alarcón C, Oskarsson T, Padua D, Wang Q, Bos PD, Gerald WL, Massagué J. (2008) Endogenous human microRNAs that suppress breast cancer metastasis. Nature 451(7175), 147-52.  [abstract]

MDACC News Release 1/16/11

MSKCC News Release 1/9/08

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Tumor resistance to the selective estrogen receptor modulator tamoxifen remains a serious clinical problem as a unifying molecular mechanism of tamoxifen resistance has remained elusive.

Researchers at UC, Denver and Tulane University examined the influence of microRNAs (miRNAs) on tamoxifen resistance in both breast tumor samples and cell models of tamoxifen resistance. They compared miRNA expression profiles of tamoxifen sensitive and tamoxifen resistant MCF-7 cells and observed significant and dramatic downregulation of miR-342 in the tamoxifen resistant cells. Expression of miR-342 was also reduced in a panel of tamoxifen refractory human breast tumors, underscoring the potential clinical importance of miR-342 downregulation.

Restoring miR-342 expression in the resistant MCF-7 cell lines sensitized these cells to tamoxifen-induced apoptosis with a dramatic reduction in cell growth. Global gene expression analysis of the restored cells by microarray identified direct and indirect targets of miR-342 not limited to those predicted in silica.

These findings suggest that miR-342 regulates tamoxifen response in breast tumor cell lines and the clinical data indicates a trend towards reduced miR-342 expression and tamoxifen resistance. In addition, the results suggest that miR-342 regulates expression of genes involved in tamoxifen mediated tumor cell apoptosis and cell cycle progression. Restoring miR-342 expression may represent a novel therapeutic approach to sensitizing and suppressing the growth of tamoxifen refractory breast tumors.

Cittelly DM, Das PM, Spoelstra NS, Edgerton SM, Richer JK, Thor AD, Jones FE. (2010) Downregulation of miR-342 is Associated with Tamoxifen Resistant Breast Tumors. Mol Cancer [Epub ahead of print]. [article]

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Epithelial to mesenchymal transition (EMT) is a key step toward metastasis. MCF7 breast cancer cells conditionally expressing the EMT master regulator SNAI1 were used to identify early expressed microRNAs (miRNAs) and their targets that may contribute to the EMT process. Potential targets of miRNAs were identified by matching lists of in silico predicted targets and of inversely expressed mRNAs. MiRNAs were ranked based on the number of predicted hits, highlighting miR-661, a miRNA with so far no reported role in EMT. MiR-661 was found required for efficient invasion of breast cancer cells by destabilizing two of its predicted mRNA targets, the cell–cell adhesion protein Nectin-1 and the lipid transferase StarD10, resulting, in turn, in the downregulation of epithelial markers. [click to continue…]

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The miR-200 family is a particularly nasty group of microRNAs. Changes in miR-200 family levels have been associated with enhanced tumorigenesis and significantly correlated with decreased survival. 

miR-200 family members are associated with resistance to several chemotherapy drugs: docetaxel  in non-small cell cancer cells1, cisplatin in breast cancer cells2, and gemcitabine in cholangiocarcinoma cells.

It has been shown that many microRNAs play an important role in regulating metastasis, the ultimate cause of death of most cancer patients, and in particular, miR-200 is responsible for direct enhancement of distant metastases of breast cancer3.

Additionally miR-200 family members are significantly over-expressed in human ovarian cancer4 and likewise are a factor in the etiology of endometriosis5.

  1. Rui W, Bing F, Hai-Zhu S, Wei D, Long-Bang C.  (2009)  Identification of microRNA profiles in docetaxel-resistant human non-small cell lung carcinoma cells (SPC-A1).  J Cell Mol Med [Epub ahead of print]  [abstract]
  2. Pogribny IP, Filkowski JN, Tryndyak VP, Golubov A, Shpyleva SI, Kovalchuk O. (2010) Alterations of microRNAs and their targets are associated with acquired resistance of MCF-7 breast cancer cells to cisplatin. Int J Cancer [Epub ahead of print] [abstract]
  3. Dykxhoorn DM, Wu Y, Xie H, Yu F, Lal A, Petrocca F, Martinvalet D, Song E, Lim B, Lieberman J.  (2009) miR-200 enhances mouse breast cancer cell colonization to form distant metastasesPLoS One 4(9), e7181.  [abstract]
  4. Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, Taccioli C, Volinia S, Liu CG, Alder H, Calin GA, Ménard S, Croce CM. (2007) MicroRNA signatures in human ovarian cancer. Cancer Res 67(18), 8699-707. [abstract]
  5. Filigheddu N, Gregnanin I, Porporato PE, Surico D, Perego B, Galli L, Patrignani C, Graziani A, Surico N. Differential expression of microRNAs between eutopic and ectopic endometrium in ovarian endometriosis. J Biomed Biotechnol 2010:369549. [abstract]

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MicroRNA Regulation of Kinase Activity

March 10, 2010

It is known that Rho-associated kinase (ROCK) signaling plays a fundamental role in regulating cell morphology, adhesion, and motility and that aberrant expression of ROCK is related to tumor metastases and poor clinical outcome. Researchers at Tufts University proposed that ROCK may enhance the metastatic propensity of breast cancer cells by promoting the c-Myc pathway, […]

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microRNA of the Week: microRNA-451

February 26, 2010

Hypoxia and monocrotaline induced strong upregulation of miR-451 suggesting a role in the development of pulmonary arterial hypertension (PAH)1, a complex disorder leading to right-sided heart failure and death. Head and neck squamous cell carcinomas (HNSCC) constitute the fifth most common malignancy worldwide. Significant downregulation of miR-451 was observed in relapsed HNSCC patients suggesting that […]

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microRNA of the week: microRNA-29

February 19, 2010

There are several groups making headlines that are studying the mir-29 family. Rosetta Genomics Headlines – Joint Study By Rosetta Genomics And NYU Langone Medical Center Identifies Single MicroRNA Biomarker For Prognosis Of Mesothelioma Patients Single microRNA exhibits potential to forecast outcomes of MPM  The results clearly demonstrate that higher levels of miR-29c* in MPM […]

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microRNA of the week: microRNA-206

February 12, 2010

When you consider that microRNAs have now been linked to almost every biological function, how is it possible that the detection of microRNAs had escaped scientists for so long? For example, a single microRNA, miR-206 with functions that range from estrogen regulation to suppression of breast cancer metastasis to regulation of neuromuscular signaling. Amazing! Williams […]

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The many complex roles of microRNA in breast cancer

February 10, 2010

There have been several studies involving microRNAs and breast cancer to date.  The findings of these studies collectively demonstrate the wide range of function that microRNA can play in just a single disease.  Researchers at Baylor College of Medicine and the University of Houston found that dysregulation of certain microRNAs have significant effect on morphological […]

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