The potential role of circular RNAs -regulated PI3K signaling in non-small cell lung cancer: Molecular insights and clinical perspective.

Non-small cell lung cancer (NSCLC), accounting for more than 80% of all cases, is the predominant form of lung cancer and the leading cause of cancer-related deaths worldwide. Significant progress has been made in diagnostic techniques, surgical interventions, chemotherapy protocols, and targeted therapies at the molecular level, leading to enhanced treatment outcomes in patients with NSCLC. Extensive evidence supports the use of circular RNAs (circRNAs), a specific category of naturally occurring non-coding small RNAs (ncRNAs), for the diagnosis, monitoring of treatment efficacy, and assessment of survival in NSCLC. CircRNAs have been identified to play significant roles in various aspects of cancer formation, either as tumor suppressors or tumor promoters, contributing to cancer development through several signaling pathways, including the phosphoinositide 3-kinases (PI3Ks) pathway. This pathway is well-established because of its regulatory role in essential cellular processes. CircRNAs regulate the PI3K/AKT pathway by targeting diverse cellular elements. This review aims to provide insight into the involvement of several circRNAs linked to the PI3K/AKT pathway in NSCLC.

Circular RNAs and cervical cancer: friends or foes? A landscape on circRNA-mediated regulation of key signaling pathways involved in the onset and progression of HPV-related cervical neoplasms.

Cervical cancer (CC) is a common gynecologic malignancy, accounting for a significant proportion of women death worldwide. Human papillomavirus (HPV) infection is one of the major etiological causes leading to CC onset; however, genetic, and epigenetic factors are also responsible for disease expansion. Circular RNAs (circRNAs), which are known as a particular subset of non-coding RNA (ncRNA) superfamily, with covalently closed loop structures, have been reported to be involved in the progression of diverse diseases, especially neoplasms. In this framework, abnormally expressed circRNAs are in strong correlation with CC pathogenesis through regulating substantial signaling pathways. Also, these RNA molecules can be considered as promising biomarkers and therapeutic targets for CC diagnosis/prognosis and treatment, respectively. Herein, we first review key molecular mechanisms, including Wnt/ß-catenin, MAPK, and PI3K/Akt/mTOR signaling pathways, as well as angiogenesis and metastasis, by which circRNAs interfere with CC development. Then, diagnostic, prognostic, and therapeutic potentials of these ncRNA molecules will be highlighted in depth.

Recent Insights into the Angioregulatory Role of Long Non-coding RNAs and Circular RNAs in Gliomas: From Signaling Pathways to Clinical Aspects.

The most prevalent and severe malignancy of the central nervous system within the brain is glioma. Glioma is a vascularized cancer, and angiogenesis is necessary for glioma growth, invasion, and recurrence. It is also believed that this factor is this factor to be accountable for therapy resistance in many cancers, including glioma. The process of angiogenesis, which plays a crucial role in both health and disease situations such as cancer, involves the creation of new blood vessels from pre-existing ones. Non-coding RNAs (ncRNAs) are unique molecules that have been found to possess a wide range of abilities to modify the expression of various genes. They carry out their gene-modulating roles at a variety of distinct levels, including post-transcriptional and post-translational levels. Long ncRNAs (lncRNAs) and circular RNAs (circRNAs) are a group of ncRNA that have attracted particular attention and are involved in the angiogenesis mechanism in cancer. Understanding the regulatory mechanisms of these RNAs in the angiogenesis process in gliomas provides unique fundamental information about the process of tumor-associated neovascularization. On the other hand, due to developments in the characterisation of lncRNAs and circRNAs, these novel structures may potentially be used in clinics as possible biomarkers for treatment strategies that target tumor angiogenesis. Throughout the review, new knowledge and views about the angioregulatory function of circRNAs and lncRNAs in gliomas have been presented. Additionally, we talk about the novel idea of ncRNA-based therapeutics for gliomas in the future.

Circular RNAs: Emerging Modulators in the Pathophysiology of Polycystic Ovary Syndrome and their Clinical Implications.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine/metabolic disorder in women of reproductive age. PCOS is characterized by hyperandrogenism, polycystic ovary morphology, and ovulatory dysfunction/anovulation. It involves multiple effects in patients, including granulosa/theca cell hyperplasia, menstrual disturbances, infertility, acne, obesity, insulin resistance, and cardiovascular disorders. Biochemical analyses and the results of RNA sequencing studies in recent years have shown a type of non-coding RNAs as a splicing product known as circular RNAs (circRNAs). Several biological functions have been identified in relation to circRNAs, including a role in miRNA sponge, protein sequestration, increased parental gene expression, and translation leading to polypeptides. These circular molecules are more plentiful and specialized than other types of RNAs. For this reason, they are referred to as potential biomarkers in different diseases. Evidence suggests that circRNAs may have regulatory potentials through different signaling pathways, such as the miRNA network. Probably most experts in the field of obstetricians are not aware of circRNAs as a useful biomarker. Therefore, this review focused on the researches that have been done on the involvement of circRNAs in PCOS and summarized recent supportive evidence, and evaluated the circRNA association and mechanisms involved in PCOS.

Unfolded Protein Response Signaling in Hepatic Stem Cell Activation in Liver Fibrosis.

Frequent exposure to various external and internal adverse forces (stresses) disrupts cell protein homeostasis through endoplasmic reticulum (ER) capacity saturation. This process leads to the unfolded protein response (UPR), which aims to re-establish/maintain optimal cellular equilibrium. This complex mechanism is involved in the pathogenesis of various disorders, such as metabolic syndrome, fibrotic diseases, neurodegeneration, and cancer, by altering cellular metabolic changes integral to activating the hepatic stellate cells (HSCs). The development of hepatic fibrosis is one of the consequences of UPR activation. Therefore, novel therapies that target the UPR pathway effectively and specifically are being studied. This article covers the involvement of the UPR signaling pathway in cellular damage in liver fibrosis. Investigating the pathogenic pathways related to the ER/UPR stress axis that contribute to liver fibrosis can help to guide future drug therapy approaches.

Non-coding RNAs in leukemia drug resistance: new perspectives on molecular mechanisms and signaling pathways.

Like almost all cancer types, timely diagnosis is needed for leukemias to be effectively cured. Drug efflux, attenuated drug uptake, altered drug metabolism, and epigenetic alterations are just several of the key mechanisms by which drug resistance develops. All of these mechanisms are orchestrated by up- and downregulators, in which non-coding RNAs (ncRNAs) do not encode specific proteins in most cases; albeit, some of them have been found to exhibit the potential for protein-coding. Notwithstanding, ncRNAs are chiefly known for their contribution to the regulation of physiological processes, as well as the pathological ones, such as cell proliferation, apoptosis, and immune responses. Specifically, in the case of leukemia chemo-resistance, ncRNAs have been recognized to be responsible for modulating the initiation and progression of drug resistance. Herein, we comprehensively reviewed the role of ncRNAs, specifically its effect on molecular mechanisms and signaling pathways, in the development of leukemia drug resistance.

Efficacy and Safety of Atezolizumab Monotherapy or Combined Therapy with Chemotherapy in Patients with Metastatic Triple-negative Breast Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: Several successful attempts have been recorded with PD-L1 blockade via atezolizumab monotherapy or combination therapy with chemotherapy in patients with metastatic triple-negative breast cancer (mTNBC). Due to the lack of a large-scale study, we present a meta-analysis aimed at evaluating the safety and efficacy of this promising strategy in patients with mTNBC. METHODS: A comprehensive literature search was conducted using electronic databases to identify eligible RCTs. Twelve studies, including 2479 mTBNC patients treated with atezolizumab monotherapy or in combination with chemotherapy, were included up to January 2022. The PRISMA checklist protocol and the I2 statistic were applied for quality assessment and heterogeneity tests of the selected trials, respectively. Fixed and random-effects models were estimated based on the heterogeneity tests, and statistical analysis was performed using CMA. RESULTS: Our pooled findings demonstrated that the median overall survival (OS) and progression-free survival (PFS) were 16.526 and 5.814 months in mTNBC patients, respectively. Furthermore, when comparing efficacy indicators between PD-L1-positive and PD-L1-negative groups, mTNBC patients with PD-L1 had better OS, PFS, and ORR than PD-L1-negative patients. Also, the immune-related adverse event incident for alopecia was higher (51.9%) than other complications across atezolizumab therapy. CONCLUSION: Moreover, the pooled analysis indicated that the overall rate of lung metastasis following atezolizumab therapy was 42.8%, which was higher than the rates of metastasis in bone (26.9%), brain (5.4%), and lymph node (6.5%). Atezolizumab showed a manageable safety profile and had promising and durable anti-tumor efficacy in TMBC patients. Higher PD-L1 expression may be closely correlated with better clinical efficacy.

Regulating miRNAs Expression by Resveratrol: Novel Insights based on Molecular Mechanism and Strategies for Cancer Therapy.

Resveratrol, a polyphenolic phytoalexin found in a wide range of plants, including grapes, berries, and peanuts, is an extensively researched phytochemical with unique pharmacological capabilities and amazing potential to affect many targets in various cancers. Resveratrol's anti-cancer activities are due to its targeting of a variety of cellular and molecular mechanisms and crucial processes involved in cancer pathogenesis, such as the promotion of growth arrest, stimulation of apoptosis, suppression of cell proliferation, induction of autophagy, regulating oxidative stress and inflammation, and improving the influence of some of the other chemotherapeutic agents. MicroRNAs (miRNAs) are non-coding RNAs that modulate gene expression by degrading mRNA or inhibiting translation. MiRNAs serve critical roles in a wide range of biological activities, and disruption of miRNA expression is strongly linked to cancer progression. Recent research has shown that resveratrol has anti-proliferative and/or pro-apoptotic properties via modulating the miRNA network, which leads to the inhibition of tumor cell proliferation, the activation of apoptosis, or the increase of traditional cancer therapy effectiveness. As a result, employing resveratrol to target miRNAs will be a unique and potential anticancer approach. Here, we discuss the main advances in the modulation of miRNA expression by resveratrol, as well as the several miRNAs that may be influenced by resveratrol in different types of cancer and the significance of this natural drug as a promising strategy in cancer treatment.

Circular RNAs: novel actors of Wnt signaling pathway in lung cancer progression.

Circular RNAs (CircRNAs) are a class of regulatory RNA transcripts, which are ubiquitously expressed in eukaryotes. CircRNA dysregulation has been shown to disrupt the interaction of the Wnt/ß-catenin pathway, which regulates several biological processes involved in tumorigenesis, thereby contributing to the development and progression of cancer. Interactions of tumor-derived circRNAs with the Wnt/ß-catenin signaling pathway provide both clinical diagnostic biomarkers and promising therapeutic targets. In this review, we outlined current evidence on the roles of circRNAs associated with the Wnt/ß-catenin pathway in regulating lung cancer formation and development. We believe that our findings will assist in the advancement or establishment of circRNA-based lung cancer therapeutic approaches.

Melatonin as a regulator of apoptosis in leukaemia: molecular mechanism and therapeutic perspectives.

Leukaemia is a dangerous malignancy that causes thousands of deaths every year throughout the world. The rate of morbidity and mortality is significant despite many advancements in therapy strategies for affected individuals. Most antitumour medications used now in clinical oncology use apoptotic signalling pathways to induce cancer cell death. Accumulated data have shown a direct correlation between inducing apoptosis in cancer cells with higher tumour regression and survival. Until now, the efficacy of melatonin as a powerful antitumour agent has been firmly established. A change in melatonin concentrations has been reported in multiple tumours such as endometrial, hematopoietic, and breast cancers. Findings show that melatonin's anticancer properties, such as its prooxidation function and ability to promote apoptosis, indicate the possibility of utilizing this natural substance as a promising agent in innovative cancer therapy approaches. Melatonin stimulates cell apoptosis via the regulation of many apoptosis facilitators, including mitochondria, cytochrome c, Bcl-2, production of reactive oxygen species, and apoptosis receptors. This paper aimed to further assess the anticancer effects of melatonin through the apoptotic pathway, considering the role that cellular apoptosis plays in the pathogenesis of cancer. The effect of melatonin may mean that it is appropriate for use as an adjuvant, along with other therapeutic approaches such as radiotherapy and chemotherapy.

A spotlight on the interplay between Wnt/ß-catenin signaling and circular RNAs in hepatocellular carcinoma progression.

Hepatocellular carcinoma (HCC) is one of the deadliest cancers due to multifocal development and distant metastasis resulting from late diagnosis. Consequently, new approaches to HCC diagnosis and treatment are required to reduce mortality rates. A large body of evidence suggests that non-coding RNAs (ncRNAs) are important in cancer initiation and progression. Cancer cells release many of these ncRNAs into the blood or urine, enabling their use as a diagnostic tool. Circular RNAs (CircRNAs) are as a members of the ncRNAs that regulate cancer cell expansion, migration, metastasis, and chemoresistance through different mechanisms such as the Wnt/ß-catenin Signaling pathway. The Wnt/ß-catenin pathway plays prominent roles in several biological processes including organogenesis, stem cell regeneration, and cell survival. Aberrant signaling of both pathways mentioned above could affect the progression and metastasis of many cancers, including HCC. Based on several studies investigated in the current review, circRNAs have an effect on HCC formation and progression by sponging miRNAs and RNA-binding proteins (RBPs) and regulating the Wnt/ß-catenin signaling pathway. Therefore, circRNAs/miRNAs or RBPs/Wnt/ß-catenin signaling pathway could be considered promising prognostic and therapeutic targets in HCC.

The Significant Role of microRNAs in Gliomas Angiogenesis: A Particular Focus on Molecular Mechanisms and Opportunities for Clinical Application.

MicroRNAs (miRNAs) are non-coding RNAs with only 20-22 nucleic acids that inhibit gene transcription and translation by binding to mRNA. MiRNAs have a diverse set of target genes and can alter most physiological processes, including cell cycle checkpoints, cell survival, and cell death mechanisms, affecting the growth, development, and invasion of various cancers, including gliomas. So optimum management of miRNA expression is essential for preserving a normal biological environment. Due to their small size, stability, and capability of specifically targeting oncogenes, miRNAs have emerged as a promising marker and new biopharmaceutical targeted therapy for glioma patients. This review focuses on the most common miRNAs associated with gliomagenesis and development by controlling glioma-determining markers such as angiogenesis. We also summarized the recent research about miRNA effects on signaling pathways, their mechanistic role and cellular targets in the development of gliomas angiogenesis. Strategies for miRNA-based therapeutic targets, as well as limitations in clinical applications, are also discussed.

Impact of polyphenols on heart failure and cardiac hypertrophy: clinical effects and molecular mechanisms.

Polyphenols are abundant in regular diets and possess antioxidant, anti-inflammatory, anti-cancer, neuroprotective, and cardioprotective effects. Regarding the inadequacy of the current treatments in preventing cardiac remodeling following cardiovascular diseases, attention has been focused on improving cardiac function with potential alternatives such as polyphenols. The following online databases were searched for relevant orginial published from 2000 to 2023: EMBASE, MEDLINE, and Web of Science databases. The search strategy aimed to assess the effects of polyphenols on heart failure and keywords were "heart failure" and "polyphenols" and "cardiac hypertrophy" and "molecular mechanisms". Our results indicated polyphenols are repeatedly indicated to regulate various heart failure-related vital molecules and signaling pathways, such as inactivating fibrotic and hypertrophic factors, preventing mitochondrial dysfunction and free radical production, the underlying causes of apoptosis, and also improving lipid profile and cellular metabolism. In the current study, we aimed to review the most recent literature and investigations on the underlying mechanism of actions of different polyphenols subclasses in cardiac hypertrophy and heart failure to provide deep insight into novel mechanistic treatments and direct future studies in this context. Moreover, due to polyphenols' low bioavailability from conventional oral and intravenous administration routes, in this study, we have also investigated the currently accessible nano-drug delivery methods to optimize the treatment outcomes by providing sufficient drug delivery, targeted therapy, and less off-target effects, as desired by precision medicine standards.

Circular RNAs: pivotal role in the leukemogenesis and novel indicators for the diagnosis and prognosis of acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy and affected patients have poor overall survival (OS) rates. Circular RNAs (circRNAs) are a novel class of non-coding RNAs (ncRNAs) with a unique loop structure. In recent years, with the development of high-throughput RNA sequencing, many circRNAs have been identified exhibiting either up-regulation or down-regulation in AML patients compared with healthy controls. Recent studies have reported that circRNAs regulate leukemia cell proliferation, stemness, and apoptosis, both positively and negatively. Additionally, circRNAs could be promising biomarkers and therapeutic targets in AML. In this study, we present a comprehensive review of the regulatory roles and potentials of a number of dysregulated circRNAs in AML.

The landscape of exosomal non-coding RNAs in breast cancer drug resistance, focusing on underlying molecular mechanisms.

Breast cancer (BC) is the most common malignancy among women worldwide. Like many other cancers, BC therapy is challenging and sometimes frustrating. In spite of the various therapeutic modalities applied to treat the cancer, drug resistance, also known as, chemoresistance, is very common in almost all BCs. Undesirably, a breast tumor might be resistant to different curative approaches (e.g., chemo- and immunotherapy) at the same period of time. Exosomes, as double membrane-bound extracellular vesicles 1) secreted from different cell species, can considerably transfer cell products and components through the bloodstream. In this context, non-coding RNAs (ncRNAs), including miRNAs, long ncRNAs (lncRNAs), and circular RNAs (circRNAs), are a chief group of exosomal constituents with amazing abilities to regulate the underlying pathogenic mechanisms of BC, such as cell proliferation, angiogenesis, invasion, metastasis, migration, and particularly drug resistance. Thereby, exosomal ncRNAs can be considered potential mediators of BC progression and drug resistance. Moreover, as the corresponding exosomal ncRNAs circulate in the bloodstream and are found in different body fluids, they can serve as foremost prognostic/diagnostic biomarkers. The current study aims to comprehensively review the most recent findings on BC-related molecular mechanisms and signaling pathways affected by exosomal miRNAs, lncRNAs, and circRNAs, with a focus on drug resistance. Also, the potential of the same exosomal ncRNAs in the diagnosis and prognosis of BC will be discussed in detail.

Melatonin targeting non-coding RNAs in cancer: Focus on mechanisms and potential therapeutic targets.

Despite, melatonin is mainly known as a regulatory factor for circadian rhythm, its notable role in other fundamental biological processes, such as redox homeostasis and programmed cell death, has been found. In this line, a growing body of evidence indicated that melatonin could apply an inhibitory effect on the tumorigenic processes. Hence, melatonin might be considered an efficient adjuvant agent for cancer treatment. Besides, the physiological and pathological functions of non-coding RNAs (ncRNAs) in various disease, particularly cancers, have been expanded over the past two decades. It is well-established that ncRNAs can modulate the gene expression at various levels. Thereby, ncRNAs can regulate the numerous biological processes, including cell proliferation, cell metabolism, apoptosis, and cell cycle. Recently, targeting the ncRNAs expression provides a novel insight in the therapeutic approaches for cancer treatment. Moreover, accumulating investigations have revealed that melatonin could impact the expression of different ncRNAs in a multiple disorders, including cancer. Therefore, in the precent study, we discuss the potential roles of melatonin in modulating the expression of ncRNAs and the related molecular pathways in different types of cancer. Also, we highlighted its importance in therapeutic application and translational medicine in cancer treatment.

Melatonin and 5-fluorouracil combination chemotherapy: opportunities and efficacy in cancer therapy.

Combined chemotherapy is a treatment method based on the simultaneous use of two or more therapeutic agents; it is frequently necessary to produce a more effective treatment for cancer patients. Such combined treatments often improve the outcomes over that of the monotherapy approach, as the drugs synergistically target critical cell signaling pathways or work independently at different oncostatic sites. A better prognosis has been reported in patients treated with combination therapy than in patients treated with single drug chemotherapy. In recent decades, 5-fluorouracil (5-FU) has become one of the most widely used chemotherapy agents in cancer treatment. This medication, which is soluble in water, is used as the first line of anti-neoplastic agent in the treatment of several cancer types including breast, head and neck, stomach and colon cancer. Within the last three decades, many studies have investigated melatonin as an anti-cancer agent; this molecule exhibits various functions in controlling the behavior of cancer cells, such as inhibiting cell growth, inducing apoptosis, and inhibiting invasion. The aim of this review is to comprehensively evaluate the role of melatonin as a complementary agent with 5-FU-based chemotherapy for cancers. Additionally, we identify the potential common signaling pathways by which melatonin and 5-FU interact to enhance the efficacy of the combined therapy. Video abstract.

Targeting Glioma Cells with Nutraceuticals: Therapeutic Effects Based on Molecular Mechanisms, New Evidence and Perspectives.

Gliomas are the most common malignant cancers of the brain that have unregulated proliferation and are known as highly invasive tumors. Hence, their relapse rate is high, and the prognosis is low. Despite remarkable advances in neuroimaging, neurosurgery, and radiation therapy, they, especially glioblastoma, are highly resistant to treatments, including radiotherapy, surgery, and temozolomide chemotherapy. The average survival rate for patients with malignant glioma is still less than two years. Accordingly, the search for new treatment options has recently become an urgent need. Today, a number of nutraceuticals have been considered because of their special role in inhibiting the angiogenic process, metastasis, and apoptosis, resulting in the inhibition of tumor growth, including glioma. Nutraceuticals can disrupt cancer cells by affecting different pathways. In fact, these compounds can reduce the growth of cancer cells, inhibit their proliferation and angiogenesis, as well as induce apoptosis in these cells and play an important role in various stages of treatment. One of the key targets of nutraceuticals may be to regulate cellular signaling pathways, such as PI3K/Akt/mTORC1, JAK/STAT, and GSK-3, or to exert their effects through other mechanisms, such as cytokine receptors and inflammatory pathways, reactive oxygen species, and miRNAs. This review refers to the results of recent studies and target molecules as well as signaling pathways affected by some nutraceuticals in glioma cells. These studies indicated that clinical trials are imminent and new approaches can be beneficial for patients.

Relationship Between Red Cell Distribution Width and Oxidative Stress Indexes in Patients with Coronary Artery Disease.

Background: Red blood cell distribution (RDW), an index of the size variability of erythrocytes, is significantly associated with coronary stenosis and can strongly predict the mortality risk in coronary artery disease (CAD). The biological mechanisms involved are not fully understood but may include oxidative stress. We sought to investigate the relationship between RDW and markers of oxidative stress in patients with CAD. Methods: Participants were 112 consecutive patients referred to department of cardiac surgery for evaluation of chest pain. 32 patients had stable CAD, 40 patients had unstable CAD and 40 subjects were diagnosed as non-CAD. The levels of lipid peroxidation (TBARS) were measured in plasma and membrane samples by a fluorometric method. The plasma levels of glutathione (GSH) and total antioxidant capacity (TAC) were determined using spectrophotometric methods. Results: Lipid peroxidation levels were significantly higher in the erythrocyte membrane of stable CAD patients than non-CAD patients. The levels of TAC were significantly lower in both stable and unstable groups when compared to that of the control group (P< 0.019 and P< 0.001, respectively), but did not differ between stable and unstable CAD. In addition, there was no significant difference in the serum GSH levels among the study groups. Membrane TBARS was directly associated with RDW in three groups of study. Conclusions: We found an independent association between RDW levels and membrane lipid peroxidation in patients with CAD. This finding suggests that oxidative stress may be a potential underlying biological mechanism for increased RDW in CAD patients.

Recent insights into the microRNA-dependent modulation of gliomas from pathogenesis to diagnosis and treatment.

Gliomas are the most lethal primary brain tumors in adults. These highly invasive tumors have poor 5-year survival for patients. Gliomas are principally characterized by rapid diffusion as well as high levels of cellular heterogeneity. However, to date, the exact pathogenic mechanisms, contributing to gliomas remain ambiguous. MicroRNAs (miRNAs), as small noncoding RNAs of about 20 nucleotides in length, are known as chief modulators of different biological processes at both transcriptional and posttranscriptional levels. More recently, it has been revealed that these noncoding RNA molecules have essential roles in tumorigenesis and progression of multiple cancers, including gliomas. Interestingly, miRNAs are able to modulate diverse cancer-related processes such as cell proliferation and apoptosis, invasion and migration, differentiation and stemness, angiogenesis, and drug resistance; thus, impaired miRNAs may result in deterioration of gliomas. Additionally, miRNAs can be secreted into cerebrospinal fluid (CSF), as well as the bloodstream, and transported between normal and tumor cells freely or by exosomes, converting them into potential diagnostic and/or prognostic biomarkers for gliomas. They would also be great therapeutic agents, especially if they could cross the blood-brain barrier (BBB). Accordingly, in the current review, the contribution of miRNAs to glioma pathogenesis is first discussed, then their glioma-related diagnostic/prognostic and therapeutic potential is highlighted briefly.