Transposon DNA sequences facilitate the tissue-specific gene transfer of circulating tumor DNA between human cells.

The exchange of genes between cells is known to play an important physiological and pathological role in many organisms. We show that circulating tumor DNA (ctDNA) facilitates cell-specific gene transfer between human cancer cells and explain part of the mechanisms behind this phenomenon. As ctDNA migrates into the nucleus, genetic information is transferred.

A retrotransposon-derived DNA zip code internalizes myeloma cells through Clathrin-Rab5a-mediated endocytosis.

Introduction: We have demonstrated that transposons derived from ctDNA can be transferred between cancer cells. The present research aimed to investigate the cellular uptake and intracellular trafficking of Multiple Myeloma-zip code (MM-ZC), a cell-specific zip code, in myeloma cell lines. We demonstrated that MM-ZC uptake by myeloma cells was concentration-, time- and cell-type-dependent.

Discovery and characterization of anti-cancer peptides from a random peptide library.

We performed a forward genetic screen to discover peptides that specifically target breast cancer cells using a Penetratin tagged, random 15mer peptide library. We identified a group of novel peptides that specifically inhibited the proliferation and survival of breast cancer cells without affecting normal primary mammary epithelial cells or fibroblasts. The intrinsic apoptotic pathway is activated by these peptides in the face of abnormal expression of numerous cell cycle regulatory genes.

hnRNPK-derived cell-penetratingpeptide inhibits cancer cell survival.

hnRNPK is a multifunctional protein that plays an important role in cancer cell proliferation and metastasis via its RNA- and DNA-binding properties. Previously we showed that cell-penetrating peptides derived from the RGG RNA-binding domain of SAFA (hnRNPU) disrupt cancer cell proliferation and survival. Here we explore the efficacy of a peptide derived from the RGG domain of hnRNPK.

Inhibiting an RBM39/MLL1 epigenomic regulatory complex with dominant-negative peptides disrupts cancer cell transcription and proliferation.

RBM39 is a known splicing factor and coactivator. Here, we report that RBM39 functions as a master transcriptional regulator that interacts with the MLL1 complex to facilitate chromatin binding and H3K4 trimethylation in breast cancer cells. We identify RBM39 functional domains required for DNA and complex binding and show that the loss of RBM39 has widespread effects on H3K4me3 and gene expression, including key oncogenic pathways.

Novel Cell-Penetrating Peptides Derived From Scaffold-Attachment- Factor A Inhibits Cancer Cell Proliferation and Survival.

Scaffold-attachment-factor A (SAFA) has important roles in many normal and pathologic cellular processes but the scope of its function in cancer cells is unknown. Here, we report dominant-negative activity of novel peptides derived from the SAP and RGG-domains of SAFA and their effects on proliferation, survival and the epigenetic landscape in a range of cancer cell types. The RGG-derived peptide dysregulates SAFA binding and regulation of alternatively spliced targets and decreases levels of key spliceosome proteins in a cell-type specific manner.

Tbx3-Mediated Regulation of Cardiac Conduction System Development and Function: Potential Contributions of Alternative RNA Processing.

In this article, we provide a brief summary of work by us and others to discover the molecular underpinnings of early conduction system development and function. We focus on how the multifunctional protein Tbx3 contributes to acquisition and homeostasis of the tissue-specific properties of the sinoatrial and atrioventricular nodes. We also provide unpublished, preliminary findings supporting the role of Tbx3-regulated alternative RNA processing in the developing conduction system.

LncRNAs Regulatory Networks in Cellular Senescence.

Long noncoding RNAs (lncRNAs) are a class of transcripts longer than 200 nucleotides with no open reading frame. They play a key role in the regulation of cellular processes such as genome integrity, chromatin organization, gene expression, translation regulation, and signal transduction. Recent studies indicated that lncRNAs are not only dysregulated in different types of diseases but also function as direct effectors or mediators for many pathological symptoms.

Discovery and Characterization of piRNAs in the Human Fetal Ovary.

Piwi-interacting RNAs (piRNAs), a class of 26- to 32-nt non-coding RNAs (ncRNAs), function in germline development, transposon silencing, and epigenetic regulation. We performed deep sequencing and annotation of untreated and periodate-treated small RNA cDNA libraries from human fetal and adult germline and reference somatic tissues. This revealed abundant piRNAs originating from 150 piRNA-encoding genes, including some exhibiting gender-specific expression, in fetal ovary and adult testis-developmental periods coinciding with mitotic cell divisions expanding fetal germ cells prior to meiotic divisions.

Long noncoding RNA PANDA and scaffold-attachment-factor SAFA control senescence entry and exit.

Cellular senescence is a stable cell cycle arrest that limits the proliferation of pre-cancerous cells. Here we demonstrate that scaffold-attachment-factor A (SAFA) and the long noncoding RNA PANDA differentially interact with polycomb repressive complexes (PRC1 and PRC2) and the transcription factor NF-YA to either promote or suppress senescence. In proliferating cells, SAFA and PANDA recruit PRC complexes to repress the transcription of senescence-promoting genes.