Tiling array and novel sequencing technologies have made available the transcription profile of the entire human genome. However, the extent of transcription and the function of genetic elements that occur outside of protein-coding genes, particularly those involved in disease, are still a matter of debate. In this review, we focus on long non-coding RNAs (lncRNAs) that are involved in cancer. We define lncRNAs and present a cancer-oriented list of lncRNAs, list some tools (for example, public databases) that classify lncRNAs or that scan genome spans of interest to find whether known lncRNAs reside there, and describe some of the functions of lncRNAs and the possible genetic mechanisms that underlie lncRNA expression changes in cancer, as well as current and potential future applications of lncRNA research in the treatment of cancer.

https://repositorium.sdum.uminho.pt/bitstream/1822/24084/1/Spizzo%20R_Oncogene%202012.pdf

Long non-coding RNAs and cancer: a new frontier of translational research?

The ultimate objective of biomedical research is to connect human diseases with the genes that underlie them and drugs that treat them. But this remains a daunting task, and even the most inspired researchers still have to resort to laborious screens of genetic or chemical libraries. What if at least some parts of this screening process could be systematized and centralized? And hits found and hypotheses generated with something resembling an internet search engine? These are the questions the Connectivity Map project set out to answer.

The Connectivity Map: a new tool for biomedical research

Role of the TMPRSS2-ERG gene fusion in prostate cancer

Recurrent gene fusions of androgen regulated genes and ETS family member genes in prostate cancer are described. Compositions and methods having utility in prostate cancer diagnosis, research, and therapy are also provided.

Recurrent gene fusions in prostate cancer

A crucial role of the immune system in cancer progression and response to therapy has recently emerged. Here, Galluzzi and colleagues discuss the immune parameters that may predict the therapeutic response of patients to chemotherapeutics, and review the mechanisms by which current antineoplastic agents activate the immune system against cancer.

The secret ally: immunostimulation by anticancer drugs

https://www.cell.com/cancer-cell/pdf/S1535-6108(06)00378-3.pdf

Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma

Background The presence of tumor-specific mutations in the cancer genome represents a potential opportunity for pharmacologic intervention to therapeutic benefit. Unfortunately, many classes of oncoproteins (e.g., transcription factors) are not amenable to conventional small-molecule screening. Despite the identification of tumor-specific somatic mutations, most cancer therapy still utilizes nonspecific, cytotoxic drugs. One illustrative example is the treatment of Ewing sarcoma. Although the EWS/FLI oncoprotein, present in the vast majority of Ewing tumors, was characterized over ten years ago, it has never been exploited as a target of therapy. Previously, this target has been intractable to modulation with traditional small-molecule library screening approaches. Here we describe a gene expression–based approach to identify compounds that induce a signature of EWS/FLI attenuation. We hypothesize that screening small-molecule libraries highly enriched for FDA-approved drugs will provide a more rapid path to clinical application.

https://dash.harvard.edu/bitstream/handle/1/4879997/1851624.pdf?sequence=1

Signature-Based Small Molecule Screening Identifies Cytosine Arabinoside as an EWS/FLI Modulator in Ewing Sarcoma

Gefitinib induces myeloid differentiation of acute myeloid leukemia.

CD8 glycoproteins are expressed as either alphaalpha homodimers or alphabeta heterodimers on the surface of T cells. CD8alphabeta is a more efficient coreceptor than the CD8alphaalpha for peptide Ag recognition by TCR. Each CD8 subunit is composed of four structural domains, namely, Ig-like domain, stalk region, transmembrane region, and cytoplasmic domain. In an attempt to understand why CD8alphabeta is a better coreceptor than CD8alphaalpha, we engineered, expressed, and functionally tested a chimeric CD8alpha protein whose stalk region is replaced with that of CD8beta. We found that the beta stalk region enhances the coreceptor function of chimeric CD8alphaalpha to a level similar to that of CD8alphabeta. Surprisingly, the beta stalk region also restored functional activity to an inactive CD8alpha variant, carrying an Ala mutation at Arg(8) (R8A), to a level similar to that of wild-type CD8alphabeta. Using the R8A variant of CD8alpha, a panel of anti-CD8alpha Abs, and three MHC class I (MHCI) variants differing in key residues known to be involved in CD8alpha interaction, we show that the introduction of the CD8beta stalk leads to a different topology of the CD8alpha-MHCI complex without altering the overall structure of the Ig-like domain of CD8alpha or causing the MHCI to employ different residues to interact with the CD8alpha Ig domain. Our results show that the stalk region of CD8beta is capable of fine-tuning the coreceptor function of CD8 proteins as a coreceptor, possibly due to its distinct protein structure, smaller physical size and the unique glycan adducts associated with this region.

/pdf/stalk-region-of-b-chain-enhances-the-coreceptor-function-of-28bmzyazp1.pdf

Jenny S. Wong

Papers

Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma

Signature-Based Small Molecule Screening Identifies Cytosine Arabinoside as an EWS/FLI Modulator in Ewing Sarcoma

Gefitinib induces myeloid differentiation of acute myeloid leukemia.

Stalk Region of β-Chain Enhances the Coreceptor Function of CD8

Expression Profiling of EWS/FLI Identifies NKX2.2 as a Critical Target Gene in Ewing's Sarcoma (DOI: 10.1016/j.ccr.2006.04.004)