To date, thousands of highly abundant and conserved single-stranded RNA molecules shaped into ring structures (circRNAs) have been identified. CircRNAs are multifunctional molecules that have been shown to regulate gene expression transcriptionally and post-transcriptionally and exhibit distinct tissue- and development-specific expression patterns associated with a variety of normal and disease conditions, including cancer pathogenesis. Over the past years, due to their intrinsic stability and resistance to ribonucleases, particular attention has been drawn to their use as reliable diagnostic and prognostic biomarkers in cancer diagnosis, treatment, and prevention. However, there are some critical caveats to their utility in the clinic. Their circular shape limits their annotation and a complete functional elucidation is lacking. This makes their detection and biomedical application still challenging. Herein, we review the current knowledge of circRNA biogenesis and function, and of their involvement in tumorigenesis and potential utility in cancer-targeted therapy.

Considering the complexity of the current framework in oncology, the relevance of animal models in biomedical research is critical in light of the capacity to produce valuable data with clinical translation. The laboratory mouse is the most common animal model used in cancer research due to its high adaptation to different environments, genetic variability, and physiological similarities with humans. Beginning with spontaneous mutations arising in mice colonies that allow for pursuing studies of specific pathological conditions, this area of in vivo research has significantly evolved, now capable of generating humanized mice models encompassing the human immune system in biological correlation with human tumor xenografts. Moreover, the era of genetic engineering, especially of the hijacking CRISPR/Cas9 technique, offers powerful tools in designing and developing various mouse strains. Within this article, we will cover the principal mouse models used in oncology research, beginning with behavioral science of animals vs. humans, and continuing on with genetically engineered mice, microsurgical-induced cancer models, and avatar mouse models for personalized cancer therapy. Moreover, the area of spontaneous large animal models for cancer research will be briefly presented.

Lung cancer is the leading disease of cancer-related deaths worldwide. Since the beginning of the 20th century, various infectious agents associated with lung cancer have been identified. The mechanisms that include systemic inflammatory pathways as effect of microbial persistence in the lung can secondarily promote the development of lung carcinogenesis. Chronic inflammation associated with lung-cancer infections is known to precede tumor development, and it has a strong effect on the response(s) to therapy. In fact, both viral and bacterial infections can activate inflammatory cells and inflammatory signaling pathways. In this review, an overview of critical findings of recent studies investigating associations between each of viral and bacterial pathogens and lung carcinoma is provided, with particular emphasis on how infectious organisms can interfere with oncogenic processes and all the way through immunity. Moreover, a discussion of the direct crosstalk between lung tumor development and inflammatory processes is also presented.

Lung cancers are broadly divided into two categories: non-small-cell lung carcinoma (NSCLC), which accounts for 80–85% of all cancer cases, and small-cell lung carcinoma (SCLC), which covers the remaining 10–15%. Recent advances in cancer biology and genomics research have allowed an in-depth characterization of lung cancers that have revealed new therapy targets (EGFR, ALK, ROS, and KRAS mutations) and have the potential of revealing even more biomarkers for diagnostic, prognostic, and targeted therapies. A new source of biomarkers is represented by non-coding RNAs, especially microRNAs (miRNAs). MiRNAs are short non-coding RNA sequences that have essential regulatory roles in multiple cancers. Therefore, we aim to investigate the tumor microenvironment (TME) and miRNA tumor profile in a subset of 51 early-stage lung cancer samples (T1 and T2) to better understand early tumor and TME organization and molecular dysregulation. We analyzed the immunohistochemistry expression of CD4 and CD8 as markers of the main TME immune populations, E-cadherin to evaluate early-stage epithelial-to-mesenchymal transition (EMT), and p53, the main altered tumor suppressor gene in lung cancer. Starting from these 4 markers, we identified and validated 4 miRNAs that target TP53 and regulate EMT that can be further investigated as potential early-stage lung cancer biomarkers.

Colon cancer-associated transcript 2 (CCAT2) is an intensively studied lncRNA with important regulatory roles in cancer. As such, cumulative studies indicate that CCAT2 displays a high functional versatility due to its direct interaction with multiple RNA binding proteins, transcription factors, and other species of non-coding RNA, especially microRNA. The definitory mechanisms of CCAT2 are its role as a regulator of the TCF7L2 transcription factor, enhancer of MYC expression, and activator of the WNT/β-catenin pathway, as well as a role in promoting and maintaining chromosome instability through the BOP1–AURKB pathway. Additionally, we highlight how the encompassing rs6983267 SNP has been shown to confer CCAT2 with allele-specific functional and structural particularities, such as the allelic-specific reprogramming of glutamine metabolism. Additionally, we emphasize CCAT2’s role as a competitive endogenous RNA (ceRNA) for multiple tumor suppressor miRNAs, such as miR-4496, miR-493, miR-424, miR-216b, miR-23b, miR-34a, miR-145, miR-200b, and miR-143 and the pro-tumorigenic role of the altered regulatory axis. Additionally, due to its upregulation in tumor tissues, wide distribution across cancer types, and presence in serum samples, we outline CCAT2’s potential as a biomarker and disease indicator and its implications for the development of resistance against current cancer therapy regiments and metastasis.

Melanoma is the most aggressive type of skin cancer. Although different anti-melanoma treatments are available, their efficacy is still improvable, and the number of deaths continues to increase worldwide. A promising source of antitumor agents could be presented by polyphenols—natural plant-based compounds. Over the past decades, many studies have described multiple anticancer effects of polyphenols in melanoma, presenting their potential interactions with targeted molecules from different signaling pathways. However, to our knowledge, there is no comprehensive review on polyphenols-regulated mechanisms in melanoma cells available in the literature. To fulfill this gap, this article aims to summarize the current knowledge of molecular mechanisms of action regulated by polyphenols involved in melanoma initiation and progression. Here, we focus on in vitro and in vivo effects of polyphenol treatments on tumor-essential cellular pathways, such as cell proliferation, apoptosis, autophagy, inflammation, angiogenesis, and metastasis. Moreover, emerging studies regarding the well-marked role of polyphenols in the regulation of microRNAs (miRNAs), highlighting their contribution to melanoma development, are also epitomized. Finally, we hope this review will provide a firm basis for developing polyphenol-based therapeutic agents in melanoma treatment.