Signal transducers and activators of transcription-3 (STAT3), a central cytoplasmic transcription factor, is frequently overexpressed and constitutively activated during malignant transformation. The overexpression of STAT3 in melanoma cells is often observed and is suggested to be involved in tumorigenesis and development. In this study, a novel antisense RNA oligonucleotides targeting the STAT3 mRNA was 2'-O-methyl modified with a 3'-butanol tag was designed, and found this uniquely modified strategy dramatic increased the stability of the RNA oligonucleotides. The results showed that the RNA oligonucleotides, namely STT-33 and STT-34, strongly inhibited the target gene expression in the melanoma cells and resulted in increase cell apoptosis. Furthermore, the RNA oligonucleotides could significantly inhibit melanoma cell proliferation and xenografts growth in nude mice. Thus, the novel modified RNA oligonucleotides targeting STAT3 may serve as a useful tool to study the involvement of STAT3 in melanoma and potentially as an anti-cancer agent for melanoma.

In the cell nucleus, DNA is wound around histone proteins, which are then packed together to form chromatin. Histones can be chemically tagged by methyl and acetyl groups. Polycomb group (PcG) proteins attach methyl groups to genes, which block their activity. This is similar to the attachment of methyl groups to gene promoters by DNA methyltransferases (DNMTs). This action is directly linked with tumor initiation and metastasis via the promotion of anti-senescence and anti-apoptosis pathways, and by facilitating epithelial mesenchymal transition (EMT). Cell fate transcriptional factors (CFTFs) and long non-coding RNAs (long ncRNAs) recruit PcG proteins to the promoters of tumor suppressor genes, resulting in epigenetic gene silencing by influencing chromatin structure and DNA accessibility. Thus, PcG proteins are potential diagnostic markers and targets for new chemoprevention and therapeutic strategies. Tumorigenesis has traditionally been considered to be driven by the sequential acquisition of mutations, leading to the activation of oncogenes and to the loss of function of tumor suppressor genes. An increasingly large amount of evidence suggests that carcinogenesis also involves "epigenetic changes", which are mediated by mechanisms that do not affect the primary DNA sequence. Epigenetic changes include both genome-wide loss and regional gain of DNA methylation, and aberrant post-translation modifications of histones. Both DNA methylation and histone modification have key functions in governing gene expression by influencing chromatin structure and DNA accessibility. Abnormal chromatin structure can cause inappropriate gene expression and genomic instability, which results in cellular transformation and malignant growth. Therefore, proteins that control chromatin structure are important in carcinogenesis. Polycomb group proteins (PcG proteins), which regulate chromatin remodeling, are one such class of proteins that regulate chromatin structure. PcG proteins form multiprotein repressive complexes, called polycomb repressive complexes (PRCs). As repressors of transcription, PRCs silence specific genes by altering chromatin modification. Here we review the biological functions and the molecular mechanisms of PcG proteins in oncogenesis. We also consider the potential role of PcG proteins in the diagnosis and treatment of cancer.