Midsize noncoding RNAs in cancers: a new division that clarifies the world of noncoding RNA or an unnecessary chaos?

Most of the human genome is made out of noncoding RNAs (ncRNAs). These ncRNAs do not code for proteins but carry a vast number of important functions in human cells such as: modification and processing other RNAs (tRNAs, rRNAs, snRNAs, snoRNAs, miRNAs), help in the synthesis of ribosome proteins, initiation of DNA replication, regulation of transcription, processing of pre-messenger mRNA during its maturation and much more. The ncRNAs also have a significant impact on many events that occur during carcinogenesis in cancer cells, such as: regulation of cell survival, cellular signaling, apoptosis, proliferation or even influencing the metastasis process. The ncRNAs may be divided based on their length, into short and long, where 200 nucleotides is the “magic” border. However, a new division was proposed, suggesting the creation of the additional group called midsize noncoding RNAs, with the length ranging from 50–400 nucleotides. This new group may include: transfer RNA (tRNA), small nuclear RNAs (snRNAs) with 7SK and 7SL, small nucleolar RNAs (snoRNAs), small Cajal body-specific RNAs (scaRNAs) and YRNAs. In this review their structure, biogenesis, function and influence on carcinogenesis process will be evaluated. What is more, a question will be answered of whether this new division is a necessity that clears current knowledge or just creates an additional misunderstanding in the ncRNA world

Biological role and diagnostic utility of ribosomal protein L23a pseudogene 53 in cutaneous melanoma

Background: Skin melanoma is one of the deadliest types of skin cancer and develops from melanocytes. The genetic aberrations in protein-coding genes are well characterized, but little is known about changes in non-coding RNAs (ncRNAs) such as pseudogenes. Ribosomal protein pseudogenes (RPPs) have been described as the largest group of pseudogenes which are dispersed in the human genome. Materials and methids: We looked deeply at the role of one of them, ribosomal protein L23a pseudogene 53 (RPL23AP53), and its potential diagnostic use. The expression level of RPL23AP53 was profiled in melanoma cell lines using qRT-PCR and analyzed based on the Cancer Genome Atlas (TCGA) data depending on BRAF status and clinicopathological parameters. Cellular phenotype, which was associated with RPL23AP53 levels, was described based on the REACTOME pathway browser, Gene Set Enrichment Analysis (GSEA) analysis as well as Immune and ESTIMATE Scores. Results: We indicted in vitro changes in RPL23AP53 level depending on a cell line, and based on in silico analysis of TCGA samples demonstrated significant differences in RPL23AP53 expression between primary and metastatic melanoma, as well as correlation between  RPL23AP53 and overall survival. No differences depending on BRAF status were observed. RPL23AP53 is associated with several signaling pathways and cellular processes. Conclusions: This study showed that patients with higher expression of RPL23AP53 displayed changed infiltration of lymphocytes, macrophages, and neutrophils compared to groups with lower expression of RPL23AP53. RPL23AP53 pseudogene is differently expressed in melanoma compared with normal tissue and its expression is associated with cellular proliferation. Thus, it may be considered as an indicator of patients' survival and a marker for the immune profile assessment

Host gene and its guest: short story about relation of long-noncoding MIR31HG transcript and microRNA miR-31

Epigenetics is the changes in a cellular phenotype without changes in the genotype. This term is not limited only to the modification of chromatin and DNA but also relates to some RNAs, like non-coding RNAs (ncRNAs), both short and long RNAs (lncRNAs) acting as molecular modifiers. Mobile RNAs, as a free form or encapsulated in exosomes, can regulate neighboring cells or be placed in distant locations. It underlines the vast capacity of ncRNAs as epigenetic elements of transmission information and message of life. One of the amazing phenomena is long non-coding microRNA-host-genes (lnc-MIRHGs) whose processed transcripts function as lncRNAs and also as short RNAs named microRNAs (miRNAs). MIR31HG functions as a modulator of important biological and cellular processes including cell proliferation, apoptosis, cell cycle regulation, EMT process, metastasis, angiogenesis, hypoxia, senescence, and inflammation. However, in most cases, the role of MIR31HG is documented only by one study and there is a lack of exact description of molecular pathways implicated in these processes, and for some of them, such as response to irradiation, no studies have been done. In this review, MIR31HG, as an example of lnc-MIRHGs, was described in the context of its known function and its potential uses as a biomarker in oncology

Biological role of long non-coding RNA in head and neck cancers

AimHead and neck squamous cell carcinoma (HNSCC) are one of the worst prognosis cancers with high mortality of patients. The treatment strategy is primarily based on surgery and radiotherapy but chemotherapy is also used. Every year the knowledge concerning HNSCC biology is updated with new elements such as the recent discovered molecules – long non-coding RNAs. Long non-coding RNAs are involved in regulatory processes in the cells. It has been revealed that the expression levels of lncRNAs are disturbed in tumor cells what results in the acquisition of their specific phenotype. lncRNAs influence cell growth, cell cycle, cell phenotype, migration and invasion ability as well as apoptosis. Development of the lncRNA panel characteristic for HNSCC and validation of specific lncRNA functions are yet to be elucidated. In this work, we collected available data concerning lncRNAs in HNSCC and characterized their biological role. We believe that the tumor examination, in the context of lncRNA expression, may lead to understanding complex biology of the cancer and improve therapeutic methods in the future

Unpredictable Changes Of Selected Mirna In Expression Profile Of Hnscc

BACKGROUND: The necessity of prediction and treatment outcome improvement of HNSCC needs to find new biomarkers. miRNAs seem to be good candidate for that. OBJECTIVE: Analysis of selected 5 miRNAs (let-7d, miR-18a, miR-21, miR-205 and miR-375) as potential biomarkers that allows to distinguish tumor and healthy tissue taken from HNSCC patients. METHODS: Tumor and normal epithelial tissues were obtained from 75 HNSCC patients to analyze selected miRNAs. RESULTS: Analysis indicated significant increase of miR-21 and miR-205 in tumor when compared with healthy tissue (p= 0.0069 and p= 0.0029, respectively). There was a significant correlation between let-7d and miR-18a. let-7d was down-regulated in 34.67% cases, miR-18a in 29.33%, miR-21 in 20%, miR-205 in 30.67% and miR-375 in 52% cases. At the same time over-expression of let-7d was detected in 18.67% cases, miR-18a in 22.67%, miR-21 in 48%, miR-205 in 41.33% and miR-375 in 52% cases. There was no correlation between miRNA expression and clinical data and the course of illness. CONCLUSION: Our study indicated that miR-21 and miR-205 can be used to analyze the clarity of surgical margins and that concomitant changes in the expression of let-7 and miR-18a in tumor tissues might represent important future markers indicating the biology of HNSCC. These observations will help with developing personalization for HNSCC patients\u27 treatment

Radio-lncRNAs: Biological Function and Potential Use as Biomarkers for Personalized Oncology

Long non-coding RNAs (lncRNAs) consist of at least 200 nucleotides. Although these molecules do not code proteins, they carry many regulatory functions in normal cells, as well as in cancer cells. For instance, many of these molecules have been previously correlated with tumorigenesis of different cancers and their reaction to various stress factors, such as radiotherapy, chemotherapy, or reactive oxygen species (ROS). The lncRNAs are associated not only with dysregulation in cancers after applied treatment but also with beneficial effects that may be achieved by modulating their expression, often significantly enhancing the patients’ outcomes. A multitude of these molecules was previously considered as potential biomarkers of tumor development, progression, or cells’ response to radio- or chemotherapy. Irradiation, which is often used in treating numerous cancer types, is not always sufficient due to cells gaining resistance in multiple ways. In this review, studies considering lncRNAs and their reaction to radiotherapy were examined. These molecules were divided regarding their role in specific processes strictly related to irradiation, and their influence on this type of treatment was explained, showing how vast an impact they have on IR-supported combat with the disease. This review aims to shed some light on potential future lncRNA-based biomarkers and therapeutic targets

Good or not good: Role of miR-18a in cancer biology

miR-18a is a member of primary transcript called miR-17-92a (C13orf25 or MIR17HG) which also contains five other miRNAs: miR-17, miR-19a, miR-20a, miR-19b and miR-92a. This cluster as a whole shows specific characteristics, where miR-18a seems to be unique. In contrast to the other members, the expression of miR-18a is additionally controlled and probably functions as its own internal controller of the cluster. miR-18a regulates many genes involved in proliferation, cell cycle, apoptosis, response to different kinds of stress, autophagy and differentiation. The disturbances of miR-18a expression are observed in cancer as well as in different diseases or pathological states. The miR-17-92a cluster is commonly described as oncogenic and it is known as ‘oncomiR-1’, but this statement is a simplification because miR-18a can act both as an oncogene and a suppressor.In this review we summarize the current knowledge about miR-18a focusing on its regulation, role in cancer biology and utility as a potential biomarker

Tumor microenvironment – Unknown niche with powerful therapeutic potential

Head and neck squamous cell carcinomas (HNSCC) are in a group of cancers that are the most resistant to treatment. The survival rate of HNSCC patients has been still very low since last 20 years. The existence of relationship between oncogenic and surrounding cells is probably the reason for a poor response to treatment. Fibroblasts are an important element of tumor stroma which increases tumor cells ability to proliferate. Another highly resistance, tumorigenic and metastatic cell population in tumor microenvironment are cancer initiating cells (CICs). The population of cancer initiating cells can be found regardless of differentiation status of cancer and they seem to be crucial for HNSCC development.In this review, we describe the current state of knowledge about HNSCC biological and physiological tumor microenvironment

Contact between European bison and cattle from the cattle breeders' perspective, in the light of the risk of pathogen transmission.

Pathogens transmitted between wildlife and domestic animals can pose a threat to endangered species, undermine conservation efforts in wildlife, and affect productivity and parasite control in domestic animals. There are several examples of pathogen transmission between European bison and other animals. The present study surveyed breeders from the vicinity of four large wisent populations in eastern Poland about observed contacts between wisent and cattle. Such contacts were noted by 37% of breeders, indicating a significant risk of contact between European bison and cattle in the study areas, even in the areas where the European bison live mainly in a forest complex, i.e., in the Borecka Forest. A higher potential risk of contacts between European bison and cattle was noted in the Białowieska Forest and the Bieszczady Mountains than in the Borecka and Knyszyńska Forests. In the Białowieska Forest, the risk of viral pathogen transmission resulting from contacts is higher (more direct contacts), and in the case of the Bieszczady Mountains, the probability of parasitic diseases is higher. The chance of contacts between European bison and cattle depended on the distance of cattle pastures from human settlements. Moreover, such contact was possible throughout the year, not only in spring and fall. It appears possible to minimize the risk of contacts between wisent and cattle by changing management practices for both species, such as keeping grazing areas as close as possible to settlements, and reducing the time cattle graze on pastures. However, the risk of contact is much greater if European bison populations are large and are dispersed beyond forest complexes