Epigenetic control of cancer by neuropeptides

Abstract

Abstract. Neuropeptides act as neurohormones, neurotransmitters and/or neuromodulators. Neuropeptides maintain physiological homeostasis and are paramount in molecular mechanisms of disease progression and regulation, including in cancer. Neuropeptides, by their definition, originate and are secreted from the neuronal cells, they are able to signal to neighboring cells or are released into the blood flow, if they act as neurohormones. The majority of neuropeptides exert their functions through G protein-coupled receptors, with certain exceptions. Although previous studies indicate that neuropeptides function in supporting proliferation of malignant cells in many types of solid tumor, the antitumorigenic action of the neuropeptides and their receptors, for example, in gastric cancers and chondrosarcoma, were also reported. It is known that epigenetically modified chromatin regulates molecular mechanisms involved in gene expression and malignant progression. The epigenetic modifications are genetically heritable, although they do not cause changes in DNA sequence. DNA methylation, histone modifications and miRNA expression are subject to those modifications. While there is substantial data on epigenetic regulation of neuropeptides, the epigenetic control of cancer by neuropeptides is considered to be uncharted territory. The aim of the current review is to describe the involvement of neuropeptides in the epigenetic machinery of cancer based on data obtained from our laboratory and from other authors.

Neuropeptides in Cancer: Friend and Foe?

“…Epigenetic modifications are further critical in regulating gene expression and controlling cancer progression. [ 266 ] Epigenetic changes are heritable throughout cell divisions, but they are reversible since the DNA sequence is not changed. DNA methylation, histone modifications, and microRNA expression are common types of epigenetic regulatory mechanisms, resulting in inaccessible DNA or nascent transcript degradation preventing the production of mature proteins.…”

Fabrication of a molecularly imprinted monolithic column via the epitope approach for the selective capillary microextraction of neuropeptides in human plasma

“…NT and the NT-related peptide neuromedin N (NmN) are synthesized from a common precursor peptide and contain the same four amino acid sequences in the C-terminal [5]. High concentrations from immunoreactive NT and NmN expressions were also found to be associated with many types of solid tumors, for example, gastric cancers, chondrosarcoma and human neuroendocrine pancreatic tumor [6]. Therefore, the simultaneous monitoring of NT and NmN concentrations in body fluids is important for clinical diagnostics and the treatment of both central and peripheral nervous system disorders [7,8].…”

The neuropeptide genes SST, TAC1, HCRT, NPY, and GAL are powerful epigenetic biomarkers in head and neck cancer: a site-specific analysis

“…Neuroendocrine peptides play essential roles in the regulation of gastrointestinal endocrine and exocrine secretion, motility, and mucosal immunity. Moreover, some neuroendocrine peptides such as gastrin , vasoactive intestinal peptide , and neurotensin have been implicated in the modulation of human tumorigenesis [ 3 , 4 ]. Most neuropeptides exert their effect through G protein-coupled receptors (GPCRs), with some exceptions [ 4 ].…”

“…Moreover, some neuroendocrine peptides such as gastrin , vasoactive intestinal peptide , and neurotensin have been implicated in the modulation of human tumorigenesis [ 3 , 4 ]. Most neuropeptides exert their effect through G protein-coupled receptors (GPCRs), with some exceptions [ 4 ]. GPCRs belong to a superfamily of cell surface signaling proteins that play a pivotal role in many physiological functions and multiple diseases [ 5 ].…”