Two Worlds Colliding: The Interplay Between Natural Compounds and Non-Coding Transcripts in Cancer Therapy

Cancer is a devastating disease and has recently become the leading cause of death in western countries, representing an immense public health burden. When it comes to cancer treatment, chemotherapy is one of the main pillars, especially for advanced stage tumors. Over the years, natural compounds have emerged as one of the most valuable resources for new chemotherapies. It is estimated that more than half of the currently used chemotherapeutic agents are derived from natural compounds. Usually, natural compounds are discovered empirically and an important limitation of introducing new anti-cancer natural products is lack of knowledge with regard to their mechanism of action. Recent data has proven that several natural compounds may function via modulating the expression and function of non-coding RNAs (ncRNAs). NcRNAs are a heterogenous class of RNA molecules which are usually not translated into proteins but have an important role in gene expression regulation and are involved in multiple tumorigenic processes, including response/resistance to pharmacotherapy. In this review, we will discuss how natural compounds function via ncRNAs while summarizing the available data regarding their effects on over 15 types of cancer. Moreover, we will critically analyze the current advances and limitations in understanding the way natural compounds exert these health-promoting effects by acting on ncRNAs. Finally, we will propose several hypotheses that may open new avenues and perspectives regarding the interaction between natural compounds and ncRNAs, which could lead to improved natural compound-based therapeutic strategies in cancer.Peer Reviewe

Editing and Chemical Modifications on Non-Coding RNAs in Cancer: A New Tale with Clinical Significance

Currently, for seemingly every type of cancer, dysregulated levels of non-coding RNAs (ncRNAs) are reported and non-coding transcripts are expected to be the next class of diagnostic and therapeutic tools in oncology. Recently, alterations to the ncRNAs transcriptome have emerged as a novel hallmark of cancer. Historically, ncRNAs were characterized mainly as regulators and little attention was paid to the mechanisms that regulate them. The role of modifications, which can control the function of ncRNAs post-transcriptionally, only recently began to emerge. Typically, these modifications can be divided into reversible (i.e., chemical modifications: m5C, hm5C, m6A, m1A, and pseudouridine) and non-reversible (i.e., editing: ADAR dependent, APOBEC dependent and ADAR/APOBEC independent). The first research papers showed that levels of these modifications are altered in cancer and can be part of the tumorigenic process. Hence, the aim of this review paper is to describe the most common regulatory modifications (editing and chemical modifications) of the traditionally considered “non-functional” ncRNAs (i.e., microRNAs, long non-coding RNAs and circular RNAs) in the context of malignant disease. We consider that only by understanding this extra regulatory layer it is possible to translate the knowledge about ncRNAs and their modifications into clinical practice

An assessment of the occupational and environmental health needs in seven Southeastern European and West-Central Asian countries

Eastern European and Central Asian countries are undergoing rapid socioeconomic and political reforms. Many old industrial facilities are either abandoned, or use outdated technologies that severely impact the environment. Emerging industries have less regulation than in developed countries and environmental and occupational problems seem to be increasing. Under a US National Institutes of Health pilot grant, we developed an interdisciplinary One Health research network in Southeastern Europe and West-Central Asia to identify environmental and occupational problems. From 2012 to 2014, this GeoHealth Hub engaged 11 academic centers and 16 public health institutions in eight different countries: Albania, Armenia, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Romania, and the United States with a goal of strengthening environmental and occupational research and training capacities. Employing face-to-face interviews and large group meetings, we conducted an evidenced-based needs and opportunities assessment focused on aquatic health, food safety, and zoonotic diseases. Comprehensive reviews of the published literature yielded priority research areas for each of the seven GeoHealth Hub countries including heavy metal and pesticide contamination, tick-borne diseases, rabies, brucellosis, and inadequate public health surveillance