February 15, 2012 at 11:00 am EST
11:00-11:05 Chairperson’s Opening Remarks
11:05-11:30 Identification of microRNAs that Negatively Regulate Prostate Cancer-Initiating Cells
Dean G. Tang, Ph.D., Professor, Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center
Like many solid tumors, prostate cancer has been shown to harbor stem-like cancer cells that possess much enhanced tumor-initiating capacity. We have recently performed a qPCR-based miRNA library screening to compare miRNA expression levels in several tumorigenic prostate cancer cell populations with the corresponding less tumorigenic subsets. This endeavor led to the identification of several tumor-suppressive miRNAs including miR-34a and let-7 to be prominently under-expressed in tumor-initiating cancer cells. Functional investigations of these miRNAs start to elucidate their distinct roles in regulating prostate cancer stem cell activities.
11:30-11:55 Non-Coding RNAs—From Bench to Bedside
George Calin, M.D., Ph.D., Associate Professor, Experimental Therapeutics, University of Texas MD Anderson Cancer Center
The newly discovered differential expression in numerous tissues, key cellular processes and multiple diseases for several families of long and short non-coding RNAs (ncRNAs—RNAs that do not codify for proteins but for RNAs with regulatory functions), including the already famous class of microRNAs (miRNAs) strongly suggest that the scientific and medical communities have significantly underestimated the spectrum of ncRNAs whose altered expression has significant consequences in diseases. microRNA and other short or long non-coding RNA alterations are involved in the initiation, progression and metastases of human cancer. The main molecular alterations are represented by variations in gene expression, usually mild and with consequences for a vast number of target protein-coding genes. The causes of the widespread differential expression of non-coding RNAs in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the processing machinery. microRNA and other short or long non-coding RNA expression profiling of human tumors has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify non-coding RNAs that may represent downstream targets of activated oncogenic pathways or that are targeting protein-coding genes involved in cancer. Recent studies proved that miRNAs and non-coding ultraconserved genes are main candidates for the elusive class of cancer-predisposing genes and that other types of non-coding RNAs participate in the genetic puzzle giving rise to the malignant phenotype. Last, but not least, the shown expression correlations of these new ncRNAs with cancer metastatic potential and overall survival rates suggest that at least some members of these novel classes of molecules could potentially find use as biomarkers or novel therapeutics in cancers and other diseases.
11:55-12:10 Sponsored Presentation
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12:10-12:35 Systems Biology and microRNA: Tools in Personalized Cancer Medicine
Asfar S. Azmi, Ph.D., Research Scientist, Department of Pathology, Wayne State University
There is a drive to develop miRNA-targeted therapies by individually targeting an miRNA thereby affecting its target genes. However, it remains unknown whether the set of miRNA target genes designated “targetome” regulated by an individual miRNA constitutes the biological network of functionally-associated molecules or reflects a random set of functionally-independent genes. Newer integrated technologies, especially systems biology, can help in deciphering these complex interacting networks and in turn can guide intelligent design of miRNA-targeted therapies for cancer. We have utilized systems science at multiple levels such as mapping de-regulated miRNA signaling in complex tumors and identifying drug response miRNA signatures of novel anti-cancer agents. Using human microRNA microarrays and Ingenuity Pathway Analysis (IPA), we have studied the target miRNA networks associated to a novel agent CDF in pancreatic cancer cells. Our analysis, utilizing the comprehensive IPA Knowledge Base, successfully extracted CDF-targeted miRNA response networks that were found to directly regulate a c-myc-p73 pro-apoptotic axis. This hub was validated at the expression level, and siRNA silencing further confirmed the role of c-myc in CDF-mediated effects. Other examples of miRNA expression signature analysis using systems technologies will be discussed. In summary it is proposed that systems biology can complement miRNA research and when combined together can benefit the development of targeted and personalized miRNA-based anti-cancer therapies.
12:35-1:00 microRNA Expression Profiling in Thyroid Cancer
Menno R. Vriens, M.D., Ph.D., Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, University Medical Center Utrecht, The Netherlands
Fine needle aspirations of thyroid nodules gives non-diagnostic or indeterminate results in ~30% of patients, and subsequent thyroid lobectomy for definitive histological diagnosis detects a malignancy in only 10-20% of the patients. microRNA expression profile is a potential diagnostic marker to distinguish benign from malignant lesions. We performed a systematic search in Medline and Embase databases until November 1, 2011, and we found 23 papers eligible for our review. Papillary, follicular, and anaplastic thyroid carcinomas were assessed. Since microRNA expression differs for normal, benign, and malignant thyroid tissue, expression analysis of differentially expressed miRNA could help distinguish benign from malignant thyroid neoplasms that are indeterminate on thyroid FNA biopsy.
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