Extracellular Biomarkers Summit, March 16-18, 2015  
Extracellular Biomarkers Summit, March 16-18, 2015 
Long Non-Coding RNA in Cancer Banner

New discoveries in the field of non-coding RNA research have led to an increased focus on understanding the role of the “Dark Genome” in cancer. Of particular interest are long non-coding RNAs, which regulate gene expression, show tissue specificity, and are deregulated in several human cancers. Newly emerging as a potential source of prognostic biomarkers, they may also aid in the early detection of disease. CHI’s Inaugural Long Non-Coding RNA in Cancer meeting will cover the exciting progress in this new frontier in genome biology.

Day 1 | Day 2 | Download Brochure 

Tuesday, March 17

12:00 pm Conference Registration


Long ncRNA as Cancer Biomarkers 

1:30 Chairperson’s Opening Remarks

Jingfang Ju, Ph.D., Associate Professor and Co-Director, Translational Research, Pathology, Stony Brook University

1:35 Non-Coding RNAs in Cancer

Carlo M. Croce, M.D., Distinguished University Professor, The John W. Wolfe Chair in Human Cancer Genetics, Director, Genetics Institute, The Ohio State University

2:25 Clinical Significance of Long Intergenic Non-Coding RNA-p21 in Colorectal Cancer

Jingfang Ju, Ph.D., Associate Professor and Co-Director, Translational Research, Pathology, Stony Brook University

Tumor suppressor p53 regulates a number of non-coding RNAs. We quantified the expression of lincRNA-p21 in colorectal cancer patients. The expression level of lincRNA-p21 was significantly lower in CRC tumor tissue. Rectum tumors showed a higher level of lincRNA-p21 than tumors in the colon. In addition, lincRNA-p21 was significantly higher in stage III than stage I tumors. Elevated levels of lincRNA-p21 were significantly associated with vascular invasion. These results suggest that lincRNA-p21 may contribute to CRC disease progression.

2:50 PCAT18 as a Novel Biomarker and Therapeutic Target in Prostate Cancer

Cheryl Helgason, Ph.D., Senior Scientist, Experimental Therapeutics, BC Cancer Research Center

We utilized RNA sequencing to identify lncRNAs differentially expressed in metastatic prostate cancer (PCa), an incurable disease. PCAT18, the most highly up-regulated transcript, is prostate and PCa specific. It is detectable in plasma and able to discriminate localized versus metastatic PCa. Functional studies demonstrate a specific role in blocking PCa cell proliferation, invasion and migration. These results position PCAT18 as a potential therapeutic target and biomarker for metastatic PCa. Additional studies have identified a potential oncosuppressive lncRNA with prognostic significance.

3:20 Refreshment Break in the Exhibit Hall with Poster Viewing


Role of lncRNA in Cancer Progression 

4:10 Chairperson’s Remarks

Richard I. Gregory, Ph.D., Associate Professor, Biological Chemistry and Molecular Pharmacology, Children’s Hospital Boston, Harvard Stem Cell Institute (HSCI), Harvard Medical School

4:15 Targeting lncRNA in Ovarian Cancer

Anil K. Sood, M.D., Professor and Vice Chairman, Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center

4:40 Role of Long Non-Coding RNAs in microRNA Regulation and Cancer

Richard I. Gregory, Ph.D., Associate Professor, Biological Chemistry and Molecular Pharmacology, Children’s Hospital Boston, Harvard Stem Cell Institute (HSCI), Harvard Medical School

It is emerging that long non-coding RNAs (lncRNAs) can have important roles in gene regulation. Dysregulation of these pathways is associated with cancer. We are investigating the role of lncRNAs in stem cell biology and cancer with a particular focus on how lncRNAs impact microRNA expression and function. Our most recent progress in this area will be presented.

5:05 Panel Discussion: What Does the Future Hold for Long Non-Coding RNA Research?

Moderator: Richard I. Gregory, Ph.D., Associate Professor, Biological Chemistry and Molecular Pharmacology, Children’s Hospital Boston, Harvard Stem Cell Institute (HSCI), Harvard Medical School

5:30 Close of Day

5:30 Short Course Registration

Recommended Dinner Short Course*

6:00-9:00 (SC3) RNA-Seq: A Fundamental Guide to the Field

*Separate registration required. View details.

 

Day 1 | Day 2 | Download Brochure 

Wednesday, March 18

7:30 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee


Linking lncRNAs to Cancer 

8:00 Chairperson’s Remarks

Myriam Gorospe, Ph.D., Senior Investigator, Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health

8:05 Senescence LncRNPs

Myriam Gorospe, Ph.D., Senior Investigator, Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health

Senescent cells accumulate in aging tissues, and their metabolic and gene expression profiles are linked to many age-related pathologies including cancer. I discuss our recent studies on the expression patterns and functions of senescence-associated long noncoding RNAs (lncRNAs), focusing on three lncRNAs differentially expressed with senescence: LincRNA-p21 (Mol Cell, 2012) which suppresses translation of select mRNAs, HOTAIR (Nat Commun, 2013), which promotes ubiquitin-mediated proteolysis of select proteins, and 7SL (Nuc Acids Res, 2014) which suppresses p53 translation.

8:30 LncRNA PVT1 Augments MYC in Human Cancers

Anindya Bagchi, Ph.D., Assistant Professor, Masonic Cancer Center, University of Minnesota

In cancers with 8q24 gain, a common mutation found in almost all human cancers, MYC is co-gained with adjacent lncRNA PVT1. We recently showed that PVT1 augments MYC in these cancers. In this lecture I will discuss the possibility of exploiting lncRNA PVT1 as a surrogate target for MYC, an otherwise undruggable cancer gene in human cancers.

8:55 Long Non-Coding RNA as Regulator of Aggressive Prostate Cancer

Dimple Chakravarty, Ph.D., Assistant Professor, Pathology, Weill Cornell Medical College

LncRNAs comprise a heterogeneous group of non-coding transcripts (>200 nt) that have emerged as key mediators of cellular homeostasis. Some lncRNAs like NEAT1 have evolved to achieve functional specialization. Our ongoing studies indicate that NEAT1 nucleates with cellular proteins to regulate fundamental like transcription and DDR. NEAT1 functions as a driver of prostate cancer progression and therapy resistance. Using a combination of next-generation sequencing and biochemical methods our studies will explain the intricate molecular mechanisms that link DDR to oncogenic modulation.

9:20 Panel Discussion

9:50 Coffee Break in the Exhibit Hall with Poster Viewing


Functional Characterization of lncRNAs 

10:30 Chairperson’s Remarks

Alexander Pertsemlidis, Ph.D., Associate Professor, Pediatrics and Cellular & Structural Biology, University of Texas Health Science Center at San Antonio

10:35 The Pivotal Role of the Oncofetal H19 lncRNA in Human Cancer

Imad Matouk, Ph.D., Senior Researcher, Laboratory of Abraham Hochberg, Hebrew University of Jerusalem

The imprinted H19 gene transcribes an onco-fetal lncRNA that is essential for human tumor growth. H19 is highly expressed in embryogenesis and cancer and serves as a precursor for miR-675. H19 is induced by hypoxic stress in a p53-dependent manner. Furthermore, numerous EMT inducers also induced H19/miR-675 expression to enhance metastasis. H19 is involved in multi-drug resistance and possesses both diagnostic and prognostic values. All of these highlight the importance of developing DNA-based therapy centered on a lncRNA system. We have successfully used regulatory elements of H19 for the treatment of bladder, ovarian, and pancreatic cancers and liver metastases in clinical trials.

11:00 Antisense Oligonucleotides for Regulation of Long Non-Coding RNA

Susan Freier, Ph.D., Vice President and Distinguished Research Fellow, Isis Pharmaceuticals

Large scale evaluation of RNA expression continues to identify an increasing number of long non-coding RNAs (lncRNA) expressed in mammalian systems. Antisense oligonucleotides (ASO) provide a straightforward method for determining function for these RNAs by specific ASO-mediated targeted degradation of the lncRNA in vitro or in vivo. MALAT1 is a ubiquitous, highly expressed, nuclear retained lncRNA with a demonstrated role in lung cancer metastasis. ASO-mediated depletion of tumor MALAT1 levels has been shown to prevent primary tumor metastasis after tumor implantation. The use of ASOs to evaluate the roles of MALAT1 and other lncRNAs in vivo will be presented.

11:25 Using ncRNAs to Identify Cancer Cell Vulnerabilities

Alexander Pertsemlidis, Ph.D., Associate Professor, Pediatrics and Cellular & Structural Biology, University of Texas Health Science Center at San Antonio

In an unbiased and comprehensive approach, we have combined a high-throughput screening platform with libraries of inhibitors of short and long non-coding RNAs. We use this platform to identify ncRNAs that reduce cell viability in general, and those that specifically sensitize cells to microtubule-targeting agents. Regulatory targets of candidate ncRNAs are identified and the response of cancer cells to perturbations in candidate ncRNA levels are assessed through a combination of in vitro, in silico and in vivo approaches.

11:50 Functional Characterization of Long Non-Coding RNAs in the p53 Tumor Suppressor Pathway

Nadya Dimitrova, Ph.D., Postdoctoral Fellow, Laboratory of Tyler Jacks, David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology

We are studying long non-coding RNAs (lncRNAs) that are directly regulated by the transcription factor p53. Using the mouse as a model organism, we have developed genetic tools to address the contribution of p53-regulated lncRNAs to this important tumor suppressor pathway. Our findings indicate a key role for lncRNAs in the transcriptional control of proteins downstream of p53 and reveal an unanticipated layer of regulation in the p53 tumor suppressor network.

BioCancell12:15 pm LUNCHEON CO-PRESENTATION: The Use of LncRNA Regulatory Elements for Innovative Anticancer Therapy; Oncofetal H19: Mechanism, Clinical Applications and Future Development
Mark L. Tykocinski, M.D., Scientific Advisory Board
Michal Gilon, Ph.D., Vice President, R&D, BioCancell
The H19 long-non-coding-RNA gene, highly and specifically expressed in a wide spectrum of tumors, is the ideal basis for highly selective anti-cancer therapy. Using the H19 regulatory elements to drive the expression of Diphtheria toxin, we have created a cancer-targeted DNA-based killing drug that leaves the healthy surrounding tissues unharmed. Our talk will review H19 mechanism of action, the creation of a “killing chromosome“ that combines H19 and IGF2 regulatory elements, and our promising clinical findings, which have lead us towards phase III clinical trial in bladder cancer. 


Epigenetic Mechanisms 

1:30 pm Chairperson’s Remarks

Subhrangsu S. Mandal, Ph.D., Associate Professor, Chemistry & Biochemistry, University of Texas Arlington

1:35 Endocrine Regulation and Disruption of Non-Coding RNAs

Subhrangsu S. Mandal, Ph.D., Associate Professor, Chemistry & Biochemistry, University of Texas Arlington

Non-coding RNAs are emerging players in regulation of gene expression and chromatin dynamics and their misregulations are associated with a variety of human diseases including cancer. Studies from our laboratory demonstrate that long non-coding RNAs (lncRNAs) are transcriptionally regulated by steroid hormones such as estrogen and potentially disrupted upon exposure to estrogenic endocrine disrupting chemicals. Here we will present our recent findings on the epigenetic mechanism of endocrine regulation and disruption of selected lncRNA in vitro and in vivo and their roles in tumorigenesis.

2:00 Epigenetic Regulation of the Human Genome by lincRNAs

Ahmad M. Khalil, Ph.D., Assistant Professor, Genetics and Genome Sciences, Case Western Reserve University School of Medicine

It is now estimated that the human genome encodes over 8,000 long intergenic non-coding RNAs (lincRNAs), but the biological functions of only a few lincRNAs have been elucidated to date. We have utilized state-of-the-art transcriptomic approaches both in vitro and in vivo to identify lincRNAs that are deregulated in several cancer types, with the hope of identifying tumor-suppressor and oncogenic lincRNAs. Subsequent functional studies are providing insights into the role of these lincRNAs in cancer initiation, progression and metastasis.

2:25 Selectively Activating Gene Expression by Targeting Long Non-Coding RNA

Caroline J. Woo, Ph.D., Scientist, RaNA Therapeutics

Long non-coding RNAs (lncRNA) can regulate transcription by recruiting epigenetic modifying complexes to target genes. PRC2, an epigenetic transcriptional repressor complex, is recruited to its target gene, via a specific lncRNA, to inhibit gene expression. We use synthetic oligonucleotides to selectively block PRC2 binding to a specific lncRNA, thereby de-repressing the expression of an mRNA, and resulting in increased amounts of the therapeutic protein.

2:50 Close of Conference



Day 1 | Day 2 | Download Brochure