The fate and function of non-coding RNAs during necroptosis.

Necroptosis is a novel form of cell death which is activated when apoptotic cell death signals are disrupted. Accumulating body of observations suggests that noncoding RNAs, which are the lately discovered mystery of the human genome, are significantly associated with necroptotic signaling circuitry. The fate and function of miRNAs have been well documented in human disease, especially cancer. Recently, lncRNAs have gained much attention due to their diverse regulatory functions. Although available studies are currently based on bioinformatic analysis, predicted interactions desires further attention, as these hold significant promise and should not be overlooked. In the light of these, here we comprehensively review and discuss noncoding RNA molecules that play significant roles during execution of necroptotic cell death.

Necroptosis is a novel form of cell death triggered by disrupted apoptotic signals. noncoding RNAs, a mystery of the human genome, are significantly associated with necroptotic signaling. Their diverse regulatory functions, particularly in cancer, warrant further attention due to their potential.

Identification of non-coding RNA signatures in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a deadly, chronic, progressive, irreversible interstitial lung disease characterized by the formation of scar tissue resulting in permanent lung damage. The average survival time following diagnosis is only 3-5 years, with a 5-year survival rate shorter than that of many cancers. Alveolar epithelial cell injury followed by irregular repair is the primary pathological process observed in patients with IPF. An evident characteristic of IPF is the development of fibroblastic foci representing active fibrotic areas. Most of the cells within these foci are believed to be myofibroblasts, which are thought to be the primary source of abnormal extracellular matrix production in IPF. The lung phenotype in IPF is characterized by significantly different processes from healthy lungs, including irregular apoptosis, oxidative stress, and epithelial-mesenchymal transition (EMT) pathways. AIMS: The exact cause of IPF is not fully understood and remains mysterious. It is not suppressing that non-coding RNAs are involved in the development and progression of IPF. Accordingly, here we aimed to identify non-coding RNA molecules during TGFß-induced myofibroblast activation. METHODS: Differential expression and functional enrichment analysis were employed to reveal the impact of non-coding RNAs during TGFß-associated lung fibrosis. RESULTS: Remarkably, LOC101448202, CZ1P-ASNS, LINC01503, IER3-AS1, MIR503HG, CLMAT3, LINC02593, ACTA2-AS1, LOC102723692, LOC107985728, and LOC105371064 were identified to be differentially altered during TGFß-stimulated myofibroblast activation. CONCLUSIONS: These findings strongly suggest that the mechanism of lung fibrosis is heavily under control of non-coding RNAs, and RNA-based therapies could be a promising approach for future therapeutic interventions to lung fibrosis.

Long non-coding RNA signatures in non-small cell lung cancer and their clinicopathological significance.

Lung cancer is the most common type of cancer in our country and worldwide, and it is a leading cause of cancer-related deaths. According to the latest global cancer statistics, lung cancer was identified as the second most common type of cancer, and the leading cause of cancer-related deaths. Long non-coding RNAs (lncRNAs) are a highly heterogeneous class of RNA molecules sharing many characteristics with mRNAs, except for the protein-coding potential. Accumulating mass of evidence suggest that lncRNAs play key regulatory roles during the multistep formation of human cancers including lung cancer. In previous studies, it has been shown that many lncRNA molecules play significant roles in the formation and progression of lung cancer. However, there are still numerous lncRNA molecules in lung cancer whose roles remain unknown. Accordingly, here we sought to ascertain the diagnostic and prognostic value of lncRNAs by analyzing the expression profiles of THRIL, NEAT1, and LOC105376095 in lung cancer. Remarkably, NEAT1 and LOC105376095 but not THRIL were identified to be differentially expressed in tissues of lung tumors. More importantly, LOC105376095, a yet uncharacterized lncRNA molecule, was significantly associated with the disease severity. Collectively, NEAT1 and LOC105376095 hold promise as potential diagnostic and prognostic biomarkers for lung cancer, presenting opportunities for targeted therapeutic interventions in the future.

ARID3A and ARID3B exert direct regulatory control over the long non-coding RNAs (lncRNAs) MALAT1 and NORAD within the context of non-small cell lung cancer (NSCLC).

Lung cancer, known for its high mortality rates and poor prognosis, remains one of the most prevalent cancer types. Early detection and effective treatment methods are crucial for improving survival rates. Non-small cell lung cancer (NSCLC) accounts for approximately 85 % of all lung cancer cases. Long non-coding RNAs (lncRNAs), which play vital roles in various biological processes, have been implicated in the development of cancer and can impact key therapeutic targets in different cancer types. In NSCLC, the dysregulation of specific lncRNAs, such as MALAT1 and NORAD, has been associated with neoplastic initiation, progression, metastasis, tumor angiogenesis, chemoresistance, and genomic instability. Both MALAT1 and NORAD directly regulate the expression of the transcription factor E2F1, thereby influencing cell cycle progression. Additionally, MALAT1 has been reported to affect the expression of p53 target genes, leading to cell cycle progression through the repression of p53 promoter activity. NORAD, on the other hand, is indirectly regulated by p53. The AT-rich interaction domain (ARID) family of DNA-binding proteins, particularly ARID3A and ARID3B, are involved in various biological processes such as cell proliferation, differentiation, and development. They also play significant roles in E2F-dependent transcription and are transcriptional targets of p53. The intricate balance between promoting cellular proliferation through the pRB-E2F pathway and inducing growth arrest through the p53 pathway underscores the crucial regulatory role of ARID3A, ARID3B, and their interaction with lncRNAs MALAT1 and NORAD. In this study, we aimed to investigate the potential interactive and functional connections among ARID3A, ARID3B, MALAT1, and NORAD in NSCLC, considering their involvement in the pRB-E2F and p53 pathways. Our findings strongly suggest that ARID3A and ARID3B play a regulatory role in controlling MALAT1 and NORAD in NSCLC. Specifically, our study demonstrates that the activities of MALAT1 and NORAD were markedly increased upon the overexpression of ARID3A and ARID3B. Therefore, we can conclude that ARID3A and ARID3B likely contribute significantly to the oncogenic functions of MALAT1 and NORAD in NSCLC. Consequently, targeting ARID3A and ARID3B could hold promise as a therapeutic approach in NSCLC, given their direct control over the expression of MALAT1 and NORAD.

The Role and Antagonistic Effects of miR-16-5p in the Regulation of ADP-Ribosylation Factor-Like Tumor Suppressor Gene 1 in Lung Cancer Cells.

OBJECTIVE: ADP-ribosylation factor-like tumor suppressor gene 1 is a member of the Ras superfamily of small guanosine triphosphatases that are known to be involved in multiple regulatory pathways in the multistage development of human cancers. Also, ADP-ribosylation factor-like tumor suppressor gene 1 expression levels have been reported to be dramatically lower in both cancer cell lines and tumor tissues compared to controls. Accordingly, defects in the regulation of the ADP-ribosylation factor-like tumor suppressor gene 1 gene seems have key tumor suppressive effects in the formation and development of human cancers including lung cancer. Moreover, microRNAs regulating the expression of ADP-ribosylation factor-like tumor suppressor gene 1 have not been described previously. Accordingly, the present study aimed to reveal the influence of miR-16-5p on the regulation of ADP-ribosylation factor-like tumor suppressor gene 1 gene. MATERIALS AND METHODS: A549 lung adenocarcinoma cells were used. For the overexpression and silencing experiments of miR-16-5p synthetic microRNA mimics and inhibitors were used, respectively. Gene expression analyses were achieved with the help of quantitative real-time polymerase chain reaction. RESULTS: MiR-16-5p was identified to be predictive target of ADP-ribosylation factor-like tumor suppressor gene 1 and directly targets the expression of ADP-ribosylation factor-like tumor suppressor gene 1 as revealed by the overexpression and silencing experiments. Specifically, it was found that miR-16-5p-overexpressed A549 cells showed a decrease in ADP-ribosylation factor-like tumor suppressor gene 1 gene expression, whereas miR16-5p-suppressed cells showed an increase in expression. These findings possibly suggest that miR-16-5p is the direct regulatory microRNA that posttranscriptionally regulates the expression of ADP-ribosylation factor-like tumor suppressor gene 1. CONCLUSION: Collectively, miR-16-5p seems to be a key regulatory molecule involved in the posttranscriptional regulation of the ADP-ribosylation factor-like tumor suppressor gene 1, and it might be responsible for the downregulation of this gene in lung cancer.

MicroRNAs and cardiac fibrosis: A comprehensive update on mechanisms and consequences.

Fibrosis is a pathological wound-healing mechanism that results by the overactivation of fibroblasts. Fibrosis can become obstructive and deleterious during regeneration of various body tissues including cardiac muscle. This ultimately results in the development of cardiac fibrosis, characterized by an excessive buildup of extracellular matrix proteins. Thus, it could lead to arrhythmias and heart failure which creates a leading public health burden worldwide. MiRNAs are small non-coding RNAs with great potential for diagnostic and therapeutic purposes. Mounting evidence indicates that miRNAs are involved in the deregulation of tissue homeostasis during myocardial fibrosis. For instance, miRNAs that are implicated in the regulation of TGF-beta signaling pathway have been reported to be significantly altered in myocardial fibrosis. Accordingly, in this comprehensive review, we discuss and highlight recent available data on the role of miRNAs during myocardial fibrosis, providing valuable insights into the miRNA modulation of cardiac fibrosis and miRNAs targets that can be used in the future therapeutic interventions to cardiac fibrosis.

Unveiling the therapeutic potential of natural-based anticancer compounds inducing non-canonical cell death mechanisms.

In the Mid-19th century, Rudolf Virchow considered necrosis to be a prominent form of cell death; since then, pathologists have recognized necrosis as both a cause and a consequence of disease. About a century later, the mechanism of apoptosis, another form of cell death, was discovered, and we now know that this process is regulated by several molecular mechanisms that "programme" the cell to die. However, discoveries on cell death mechanisms are not limited to these, and recent studies have allowed the identification of novel cell death pathways that can be molecularly distinguished from necrotic and apoptotic cell death mechanisms. Moreover, the main goal of current cancer therapy is to discover and develop drugs that target apoptosis. However, resistance to chemotherapeutic agents targeting apoptosis is mainly responsible for the failure of clinical therapy and adverse side effects of the chemotherapeutic agents currently in use pose a major threat to the well-being and lives of patients. Therefore, the development of natural-based anticancer drugs with low cellular and organismal side effects is of great interest. In this comprehensive review, we thoroughly examine and discuss natural anticancer compounds that specifically target non-canonical cell death mechanisms.

Evaluation of cytotoxic, antifungal, and larvicidal activities of different bis-sulfonamide Schiff base compounds.

Schiff bases (imines or azomethines) are versatile ligands synthesized from the condensation of amino compounds with active carbonyl groups and used for many pharmaceutical and medicinal applications. In our study, we aimed to determine the cytotoxic, antifungal and larvicidal activities of biologically potent bis-sulfonamide Schiff base derivatives that were re-synthesized by us. For this aim, 16 compounds were re-synthesized and tested for their cytotoxic, antifungal and larvicidal properties. Among this series, compounds A1B2, A1B4, A4B2, A4B3, and A4B4 were shown to have cytotoxic activity against tested cancer lung cell line (A549). The most potent antifungal activity was observed in compounds A2B1 and A2B2 against all fungi. A1B1 showed the strongest larvicidal effect at all concentrations at the 72nd h (100% mortality). These obtained results demonstrate that these type of bis-substituted compounds might be used as biologically potent pharmacophores against different types of diseases.

Inflammation-associated long non-coding RNA signature in radicular cyst tissues.

Radicular cysts are characterized by significant levels of changes in inflammatory biomarkers. Among them, interleukins and growth factors have been reported to be deregulated in radicular cyst tissues. Moreover, long non-coding RNAs are recently discovered non-coding RNA molecules that regulate various intracellular stimuli to keep homeostasis in balance. A growing body of evidence suggests that lncRNAs are significantly involved in the regulation of inflammation by targeting various inflammatory biomarkers. Accordingly, the present study was aimed to investigate the gene expression levels of inflammation-related lncRNAs in radicular cysts and show their possible roles in the development of radicular cysts. For the study, a total of 25 patients with a radiologically and pathologically confirmed radicular cyst were enrolled. For the determination of non-coding RNA expression levels, real-time qPCR was used. As a result of the current study, expression levels of PACER and THRIL were found to be significantly elevated in radicular cyst tissues compared to control tissue samples. However, MALAT1, ANRIL, and NEAT1 expression levels were not significantly altered in radicular cyst tissues compared to control tissue samples. In conclusion, long non-coding RNAs, PACER and THRIL, seem to have significant pathophysiological roles by acquiring molecular changes during inflammation and might be involved in the development and formation of radicular cysts.

The roles of long non-coding RNAs in the necroptotic signaling of colon cancer cells.

BACKGROUND: Necroptosis is a controlled form of necrosis which can be stimulated in cases where the apoptosis signal is absent. Necroptosis can be induced by DR family ligands and by various intracellular and extracellular stimuli that triggers the activation of DR family ligands. Necrostatins, which are specific RIP1 antagonists, prevent necroptosis by inhibiting RIP1 kinase, allowing survival and propagation of cells in the presence of DR ligands. Furthermore, there is a mounting evidence that long non-coding RNA (lncRNA) molecules accomplish vital functions in cell death processes such as apoptosis, autophagy, pyroptosis, and necroptosis. Accordingly, here we aimed to decipher the lncRNAs that are involved in the control and maintenance of necroptosis signaling. METHODS AND RESULTS: Colon cancer cell lines, HT-29 and HCT-116 were used for the study. For the chemical modulation of necroptosis signaling, 5-Fluorouracil, TNF-α and/or Necrostatin-1 were used. Gene expression levels were determined by quantitative real-time PCR. Remarkably, lncRNA P50-associated COX-2 extragenic RNA (PACER) was identified to be suppressed in necroptosis-induced colon cancers, whereas the expression of PACER was restored when necroptosis was suppressed. In addition, no detectable change was observed in HCT-116 colon cancer cells, as these cells lack the expression of RIP3 kinase. CONCLUSIONS: Collectively, current findings clearly imply that PACER have key regulatory roles in the control of necroptotic cell death signaling circuitry. Notably, the tumor promoter activity of PACER might be responsible for the lack of necroptotic death signal in cancer cells. Also, RIP3 kinase seems to be essential component in PACER-associated necroptosis.

Wound healing activity of Salvia huberi ethanolic extract in streptozocin-induced diabetic rats.

Objective: The aim of this study was to examine the in vivo wound healing potential of Salvia huberi Hedge (endemic to Turkey) on excision and incision wound models in diabetic rats. Method: Male Wistar albino rats, 3-4 months old and weighing 180-240g were used. The animals were randomly divided into five groups including Control, Vehicle and Fito reference, and two different concentrations (0.5% and 1% weight/weight (w/w)) of ethanol extract of Salvia huberi were investigated in both wound models on streptozocin-induced diabetic rats using macroscopic, biomechanical, biochemical, histopathological, genotoxic and gene expression methods over both seven and 14 days. Fito cream (Tripharma Drug Industry and Trade Inc., Turkey) was used as the reference drug. Results: A total of 60 rats were used in this study. Salvia huberi ointments at 0.5% and 1% (w/w) concentrations and Fito cream showed 99.3%, 99.4% and 99.1% contraction for excision wounds, and 99.9%, 97.0% and 99% contraction for incision wounds, respectively. In Salvia huberi ointments and Fito cream groups, re-epithelialisation increased dramatically by both day 7 and day 14 (p<0.05). By day 14, low hydroxyproline and malondialdehyde (MDA) levels, and high glutathione (GSH) levels were observed in the Salvia huberi ointment groups. After two application periods, damaged cell percent and genetic damage index values and micronucleus frequency of Salvia huberi ointment treatment groups were lower than Control and Vehicle groups (p<0.001). A growth factor expression reached a high level by day 7 in the Control group; in Salvia huberi-treated groups it was decreased. Conclusion: The study showed that application of Salvia huberi ointments ameliorated the healing process in diabetic rats with excisional and incisional wounds and may serve as a potent healing agent.

Expression pattern of hypoxia-related genes in odontogenic cysts.

OBJECTIVE: The aim of the present study was to reveal the effects of hypoxia-associated signaling in odontogenic cysts. DESIGN: The expression levels of genes involved in the hypoxia-associated signaling pathway were determined by quantitative Polymerase Chain Reaction (PCR) method. RESULTS: As a result, it was found that phosphatase and tensin homolog (PTEN) expression was low (p = 0.037), and the expression levels of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) (p = 0.0127), hypoxia inducible factor 1 alpha (HIF1A) (p < 0.001), and HIF1A antisense RNA 1 (HIF1A-AS1) (p = 0.0218) were higher in cyst tissue compared to normal tissue. HIF1A gene expression was found to be significantly altered according to the pathologic subtypes of odontogenic keratocyst, dentigerous cyst, and radicular cyst. CONCLUSIONS: Odontogenic cysts were found to have higher expression of HIF1A and HIF1A-AS1, which may be related to the increased hypoxia in these lesions. In addition, PI3K/Akt signaling may be stimulated by increased PIK3CA and decreased PTEN expression, which promote cell survival and support the mechanism of cyst formation.

Novel zinc oxide nanoparticles of Teucrium polium suppress the malignant progression of gastric cancer cells through modulating apoptotic signaling pathways and epithelial to mesenchymal transition.

Management of gastric cancer is still challenging due to resistance to current chemotherapeutics and recurrent disease. Moreover, green- synthesized zinc oxide nanoparticles (ZnO-NPs) using natural resources are one of the most promising therapeutic agents for anticancer therapy. Here we report the facile green synthesis and characterization of ZnO-NPs from Teucrium polium (TP-ZnO-NP) herb extract and the anticancer activities of these nanoparticles on gastric cancer cells. Facile green synthesis of TP-ZnO-NP was achieved using zinc acetate dihydrate. For the characterization of TP-ZnO-NP, UV-vis spectroscopy, FTIR, SEM, XRD and EDX analyses were performed. Antiproliferative and anticancer activities of TP-ZnO-NP were explored using the HGC-27 gastric cancer cell line model. MTT cell viability and colony formation assays were used for the analysis of cell proliferation and migration. Wound healing assay was used to analyze the migration capacities of cells. Annexin V/PI double staining, DNA ladder assay, and Acridine orange/Ethidium bromide staining were performed to analyze the induction of apoptosis. qPCR was used to determine gene expression levels of apoptotic and epithelial to mesenchymal transition marker genes. The aqueous extract of TP served as both a reducing and capping agent for the successful biosynthesis of zinc oxide nanoparticles. Remarkably, synthesized TP-ZnO-NPs were found to have significant antiproliferative and anticancer activities on HGC-27 gastric cancer cells. Collectively, current data suggest that TP-ZnO-NP is a novel and promising anticancer agent for future therapeutic interventions in gastric cancer.

Non-coding RNA variations in oral cancers: A comprehensive review.

For a long time, scientists believed that only changes or mutations in protein-coding genes were responsible for the onset and development of cancer. However, the discovery of non-coding RNAs has revolutionized our understanding of tumor biology. Now, we are aware that non-coding RNA molecules have a higher influence on cancer biology than previously thought. The discovery of non-coding RNAs also presented several challenges because they are relatively unstable under laboratory conditions and can lead to false-positive and false-negative results in expression analysis. Therefore, variation analysis may provide more accurate results for understanding the role and impact of these molecules in cancer biology. Accordingly, in the present comprehensive review, we aimed to review and discuss current knowledge on non-coding RNA alterations linked to the development and progression of oral malignancies. Collectively, variations of non-coding RNA molecules seem to have great impact in the development and progression of oral cancers.

Salivary gland tumors exhibit distinct miRNA signatures involved in Wnt/ß-Catenin signaling in formalin fixed paraffin embedded tissue samples.

Advances in high-throughput genomic technologies have enabled the identification of numerous selective tumor markers. However, adapting these newly identified markers to clinical practice is not always possible because most RNA molecules, including mRNAs of protein-coding genes and long non-coding RNAs, are not stable under laboratory conditions, making their testing a major challenge. In contrast to long RNA molecules, miRNAs offer a great advantage in that they are relatively stable due to their small size. Accordingly, herein we aimed to determine the expression levels of miRNAs that are involved in Wnt/ß-catenin signaling pathway in formalin fixed paraffin embedded (FFPE) tissue samples of patients with salivary gland tumors. A total of 42 patients with salivary gland tumors were included in the study. The miRNA expression signatures were evaluated using the RT-qPCR. As a result, ß-catenin positivity was observed in all salivary gland tumors without distinguishing between benign and malignant phenotypes. Remarkably, we found that miR-200a and miR-373 were significantly upregulated whereas miR-30c were downregulated in tissues of patients with salivary gland tumors, compared to adjacent healthy tissue samples. In addition, distinct expression signatures of these miRNAs were significantly associated with the clinicopathological findings of patients such as perineural invasion and lymph node metastasis. Additionally, miR-145 and miR-30a were found to be specifically downregulated in a mucoepidermoid carcinoma. Also, miR-26b was selectively increased in pleomorphic adenomas of the salivary gland. Collectively, our findings suggest that these miRNAs may play chief roles in the differential diagnosis of salivary gland tumors.

Asprosin, a C-Terminal Cleavage Product of Fibrillin 1 Encoded by the FBN1 Gene, in Health and Disease.

Background: Asprosin is a novel fasting-induced, glucogenic, and orexigenic protein hormone that is discovered with the help of genetic studies in patients with neonatal progeroid syndrome. Asprosin is encoded by the penultimate 2 exons (65 and 66) of the fibrillin 1 (FBN1) gene. Profibrillin 1 is the unprocessed protein product of FBN1 and undergoes a proteolytic cleavage by furin enzyme to produce mature fibrillin 1 and asprosin. The main organ responsible for the asprosin production seems to be white adipose tissue. Summary: Asprosin promotes hepatic glucose release in the liver and appetite stimulation in the hypothalamus through activation of the cAMP signaling circuitry through interacting with its G protein-coupled receptor, called OR4M1. Increasing mass of evidence suggests that asprosin is involved in the development and progression of various clinical conditions including diabetes, obesity, cardiomyopathy, cancer, and polycystic ovarian syndrome. It regulates various cellular and physiological processes such as appetite stimulation, glucose release, insulin secretion, apoptotic cell death, and inflammatory response. In this review, we discuss the current literature on asprosin and try to shed light on the yet undiscovered functions of asprosin. Key Message: Asprosin is a key regulatory factor for preserving the homeostasis of energy metabolism.

Deciphering miRNAs associated with cellular stress response and apoptosis mechanisms regulated by p53 activity in patients with lower lip cancer.

Cancers of the lips and oral cavity are a leading cause of death worldwide. Although they account for only 2% of the global cancer burden, they significantly affect the comfort of patients and eventually lead to a person's death. Also, defects in the cellular stress response and apoptosis mechanisms regulated by p53 activity is an important hallmark of cancer cells. Here, we aimed to decipher miRNAs associated with cellular stress response and apoptosis mechanisms regulated by p53 activity in patient with lower lip cancer and reveal the association of these miRNAs with the clinical course of the disease. The present research included a total of 40 eligible individuals with pathologically confirmed lower lip cancer diagnosis. Formalin-fixed, paraffin-embedded (FFPE) tissue samples of patients were obtained, and miRNAs expressions were analyzed by qPCR. Immunohistochemistry was used to determine p53 and Ki67 expression status. While three of these miRNAs (miR-130a, -375, and -128a) were found to be elevated in tumor cells compared to normal tissues of lower lip cancer patients, five were downregulated (let-7a, -7b, -7c, and miR-138, -23a), but only three were significantly altered. Particularly, we identified three miRNA signatures in which miR-128a was significantly upregulated and miR-23a and let-7c were significantly downregulated in patients with lower lip cancer. Remarkably, let-7c identified to be a promising prognostic factor for lip cancer. Our findings demonstrate that these miRNAs play important regulatory roles in lower lip cancer pathobiology, highlighting their potential relevance in diagnosis and prognosis of these patients. Moreover, these miRNAs can be targeted in future therapeutic interventions against lower lip cancer.

Non-coding RNAs transcribed from ultra-conserved regions (T-UCRs) are differentially expressed in dental follicle tissues of impacted mandibular third molars.

INTRODUCTION: Transcribed ultra-conserved regions (T-UCRs) are a new class of long non-coding RNA molecules transcribed from ultra-conserved regions (UCRs) of the human genome. T-UCRs are extremely conserved in the human, rat, and mouse genomes. Deletions of genomic areas containing UCRs resulted in live mice that developed without distinguishable phenotypes, implying that T-UCRs are involved in developmental processes. In addition, there is increasing evidence that dental follicle tissues exhibit various cellular alterations involving deregulation of protein-coding genes and non-coding RNAs. Accordingly, the main objective of the present study was to determine the clinical significance and distinct expression signatures of non-coding RNA molecules transcribed from ultra-conserved regions in dental follicle tissues of impacted mandibular third molars. MATERIALS AND METHODS: From March 2021 to December 2021, a total of 42 patients who referred to clinic of oral and maxillofacial surgery department with the indications of impacted mandibular third molar extraction from 38th and 48th positions were enrolled for the study. For the analysis of T-UCR expression levels, real-time quantitative reverse transcription PCR method was used. RESULTS: Findings of the present study indicated that T-UCRs are distinctly expressed in dental follicle tissues of impacted mandibular third molars. The expression of uc.38, uc.112, and uc.338 was found to be significantly increased in the dental follicles of impacted mandibular third molars, indicating a clinical significance of these molecules. In addition, no differences in T-UCR expression were found as a function of demographic characteristics. CONCLUSIONS: Collectively, transcribed ultra-conserved elements, such as uc.38, uc.112, and uc.338, are considerably deregulated in the dental follicle tissues of impacted mandibular third molars and might be responsible for the molecular changes acquired by dental follicle tissues of impacted mandibular third molars.

The dark matter of the human genome and its role in human cancers.

The transcribed ultra-conserved regions (T-UCRs) are a novel family of non-coding RNAs which are absolutely conserved (100%) across orthologous regions of the human, mouse, and rat genomes. T-UCRs represent a small portion of the human genome that is likely to be functional but does not code for proteins and is referred to as the "dark matter" of the human genome. Although T-UCRs are ubiquitously expressed, tissue- and disease-specific expression of T-UCRs have also been observed. Accumulating evidence suggests that T-UCRs are differentially expressed and involved in the malignant transformation of human tumors through various genetic and epigenetic regulatory mechanisms. Therefore, T-UCRs are novel candidate predisposing biomarkers for cancer development. T-UCRs have shown to drive malignant transformation of human cancers through regulating non-coding RNAs and/or protein coding genes. However, the functions and fate of most T-UCRs remain mysterious. Here, we review and highlight the current knowledge on these ultra-conserved elements in the formation and progression of human cancers.

Differential Expression of Long Noncoding RNAs in Patients with Coronary Artery Disease.

Long noncoding RNAs (lncRNAs) constitute the largest class of noncoding RNAs and play significant roles in the development of cardiovascular pathologies. In the present study, we aimed to evaluate whether 4 candidate lncRNAs - MIAT, MEG3, MALAT1, and MCM3AP-AS1 - have distinct expression levels in patients with obstructive coronary artery disease (CAD) and reveal the diagnostic and therapeutic potentials of these lncRNAs for CAD. A total of 90 patients who subjected to coronary angiography were enrolled. Relative expression of lncRNAs were assayed using qRT-PCR methodology. As a result, MIAT was downregulated, while MEG3 was upregulated in CAD patients. Receiver operating characteristic curves demonstrated that these lncRNAs have a high potential to provide sensitive and specific diagnosis of CAD. The calculated area under curve levels indicated that MIAT and MEG3 have high diagnostic value for detecting the presence of significant CAD. However, MALAT1 and MCM3AP-AS1 levels were not sufficiently reliable for CAD development in our cases. Here, we demonstrate that MIAT and MEG3 were differentially expressed in our patients and might be promising biomarkers and therapeutic targets for CAD. These results indicate that MIAT and MEG3 could play chief roles in CAD development.