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Circular RNAs (circRNAs) have emerged as critical regulators in cancer biology, contributing to various cancer hallmarks, including cell proliferation, apoptosis, metastasis, and drug resistance. Defined by their covalently closed loop structure, circRNAs possess unique characteristics like high stability, abundance, and tissue-specific expression. These non-coding RNAs function through mechanisms such as miRNA sponging, interactions with RNA-binding proteins (RBPs), and modulating transcription and splicing. Advances in RNA sequencing and bioinformatics tools have enabled the identification and functional annotation of circRNAs across different cancer types. Clinically, circRNAs demonstrate high specificity and sensitivity in samples, offering potential as diagnostic and prognostic biomarkers. Additionally, therapeutic strategies involving circRNA mimics, inhibitors, and delivery systems are under investigation. However, their precise mechanisms remain unclear, and more clinical evidence is needed regarding their roles in cancer hallmarks. Understanding circRNAs will pave the way for novel diagnostic and therapeutic approaches, potentially improving patient outcomes., Competing Interests: Declaration of Competing Interest The authors declare they have no conflict of interest, (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Schizophrenia is a mental condition that impairs several aspects of brain function and behavior. Recent investigations highlighted abnormal function of numerous genes in this context. Notably, genes that affect oxidative stress and neuron damage were the focus of several studies. In an attempt to find a biomarker that can be quantified in the peripheral blood, we assessed blood expression of three lncRNAs that were associated with these processes in patients with schizophrenia and matched controls. We observed a statistically significant downregulation of SNHG5 in the patient group compared to healthy controls, with P-values of < 0.0001, 0.0008, and 0.003 in total, male, and female patients, respectively. LINC-PINT was also found to be down-regulated in all comparisons between patients and controls with P-values of < 0.0001, < 0.0001 and = 0.01, in total, male, and female patients, respectively. However, statistical analyses disclosed no notable difference in the expression of TP53TG1 between study subgroups. Most notably, LINC-PINT and SNHG5 could discriminate between patients and controls with acceptable AUC and specificity values. Cumulatively, the results of this study propose down-regulation of LINC-PINT and SNHG5 as a possible peripheral indicator of the presence of schizophrenia., Competing Interests: Declarations. Competing Interest: The authors declare no competing interests. Ethical Approval: All procedures were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments. Consent to Participant: Informed consent forms were obtained from all study participants and from legally authorized representative/next of kin of deceased patients. The study protocol was approved by the ethical committee of Shahid Beheshti University of Medical Sciences. Consent to Publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Stem-cell therapy is a revolutionary frontier in modern medicine, offering enormous capacity to transform the treatment landscape of numerous debilitating illnesses and injuries. This review examines the revolutionary frontier of treatments utilizing stem cells, highlighting the distinctive abilities of stem cells to undergo regeneration and specialized cell differentiation into a wide variety of phenotypes. This paper aims to guide researchers, physicians, and stakeholders through the intricate terrain of stem-cell therapy, examining the processes, applications, and challenges inherent in utilizing stem cells across diverse medical disciplines. The historical journey from foundational contributions in the late 19th and early 20th centuries to recent breakthroughs, including ESC isolation and iPSC discovery, has set the stage for monumental leaps in medical science. Stem cells' regenerative potential spans embryonic, adult, induced pluripotent, and perinatal stages, offering unprecedented therapeutic opportunities in cancer, neurodegenerative disorders, cardiovascular ailments, spinal cord injuries, diabetes, and tissue damage. However, difficulties, such as immunological rejection, tumorigenesis, and precise manipulation of stem-cell behavior, necessitate comprehensive exploration and innovative solutions. This manuscript summarizes recent biotechnological advancements, critical trial evaluations, and emerging technologies, providing a nuanced understanding of the triumphs, difficulties, and future trajectories in stem cell-based regenerative medicine. Future directions, including precision medicine integration, immune modulation strategies, advancements in gene-editing technologies, and bioengineering synergy, offer a roadmap in stem cell treatment. The focus on stem-cell therapy's potential highlights its significant influence on contemporary medicine and points to a future in which individualized regenerative therapies will alleviate various medical disorders., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Active neutrophils play a variety of roles in both innate and adaptive immune responses, and one of the most vital roles is the formation and release of neutrophil extracellular traps (NETs). NETs are created when neutrophils release their chromatin contents to get and eradicate pathogenic organisms essentially. While NET helps fight bacteria, viruses, parasites, and infections, it is also linked to asthma, atherosclerosis, and cancer metastasis. Thus, understanding the molecular mechanisms behind NETosis formation and its inhibition is crucial for developing safe and effective therapies. This systematic review aims to identify the list of miRNAs that are associated with the formation of NETosis and illustrate the mechanism of action by classifying them based on their expression site. Moreover, it summarizes the list of miRNAs that can be targeted therapeutically to reduce NETosis in various disorders. The current study entailed the searching of PubMed and Google Scholar for articles related to the research topic role of miRNAs in NETosis in all types of disorders. The search terms and phrases included "NETs," "neutrophil extracellular traps," "NETosis," "miRNA," "miR," and "micro-RNA." The search was limited to articles published in English since October 2024 in both databases. Following a review of 23 papers, 19 of them met the inclusion and exclusion criteria of this study. Four papers have been removed as they are duplicated or do not meet our criteria. According to the published articles till October 2024, there are 14 miRNAs involved in the molecular pathway of NETosis which are miR-155, miR-1696, miR-7, miR-223, miR-146a, miR-142a-3p, miR-3146, miR-505, miR-4512, miR-15b-5p, miR-16-5p, miR-26b-5p, miR-125a-3p and miR-378a-3p. Moreover, eight miRNAs have been identified as possible therapeutic targets for the suppression of NETosis based on in-vivo studies carried out in various organisms, which are miR-155, miR-146a, miR-1696, miR-223, miR-142a-3p, miR-3146, miR-4512, miR-16-5p. Different miRNAs that are expressed inside or outside of neutrophils can regulate and influence NETosis. Eight miRNAs have also been identified as potential therapeutic targets, which can be utilized to inhibit the molecular pathways associated with NETosis and prevent its negative effects, such as asthma, atherosclerosis, cancer metastasis, and cancer recurrence. However, further human-based research is necessary to completely understand the role of miRNAs in the development of NETosis in humans., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Respiratory disorders are among the conditions that affect the respiratory system. The healthcare sector faces challenges due to the emergence of drug resistance to prescribed medications for these illnesses. However, there is a technology called CRISPR/Cas9, which uses RNA to guide DNA targeting. This technology has revolutionized our ability to manipulate and visualize the genome, leading to advancements in research and treatment development. It can effectively reverse epigenetic alterations that contribute to drug resistance. Some studies focused on health have shown that targeting genes using CRISPR/Cas9 can be challenging when it comes to reducing drug resistance in patients with respiratory disorders. Nevertheless, it is important to acknowledge the limitations of this technology, such as off-target effects, immune system reactions to Cas9, and challenges associated with delivery methods. Despite these limitations, this review aims to provide knowledge about CRISPR/Cas9 genome editing tools and explore how they can help overcome resistance in patients with respiratory disorders. Additionally, this study discusses concerns related to applications of CRISPR and provides an overview of successful clinical trial studies., (© 2024. The Author(s).)

Cancer is a broad name for a group of diseases in which abnormal cells grow out of control and are characterized by their complexity and recurrence. Although there has been progress in cancer therapy with the entry of precision medicine and immunotherapy, cancer incidence rates have increased globally. Non-coding RNAs in the form of circular RNAs (circRNAs) play crucial roles in the pathogenesis, clinical diagnosis, and therapy of different diseases, including cancer. According to recent studies, circRNAs appear to serve as accurate indicators and therapeutic targets for cancer treatment. However, circRNAs are promising candidates for cutting-edge cancer therapy because of their distinctive circular structure, stability, and wide range of capabilities; many challenges persist that decrease the applications of circRNA-based cancer therapeutics. Here, we explore the roles of circRNAs as a replacement for cancer therapy, highlight the main challenges facing circRNA-based cancer therapies, and discuss the key strategies to overcome these challenges to improve advanced innovative therapies based on circRNAs with long-term health effects., Competing Interests: The authors declare they have no conflict of interest., (© 2024 The Authors.)

Obesity is a worldwide health problem with an increasing trend. This condition has a significant genetic background. H19 lncRNA has been shown to protect from dietary obesity through decreasing levels of monoallelic genes in brown fat. In the current study, we aimed to find the association between two possibly functional H19 polymorphisms, namely rs217727 and rs2839698 and obesity in Iranian population. These polymorphisms have been shown to affect risk of some obesity-related conditions in different populations. The study included 414 obese cases and 392 controls. Notably, both rs2839698 and rs217727 were associated with obesity in the allelic model as well as all supposed inheritance models. In addition, after adjustment for gender, all P values remained significant. For rs2839698, the OR (95% CI) for T allele vs. C allele was 3.29 (2.67-4.05) (P-value < 0.0001). In the co-dominant model, both TT and CT genotypes were found to confer risk of obesity compared with CC genotype (OR (95% CI)= 14.02 (8.39-23.43) and 9.45 (6.36-14.04), respectively). Similarly, combination of TT and CT genotypes had an OR (95% CI) = 10.32 (7.03-15.17) when compared with CC genotype. For rs217727, the T allele was found to exert a protective effect (OR (95% CI) = 0.6 (0.48-0.75)). Moreover, in the co-dominant model, OR (95% CI) values for TT and TC genotypes vs. CC genotype were 0.23 (0.11-0.46) and 0.65 (0.49-0.87), respectively. Taken together, H19 polymorphisms may affect risk of obesity in Iranian population. It is necessary to conduct functional studies to confirm a causal relationship between the rs217727 and rs2839698 polymorphisms and obesity., (© 2023. The Author(s).)

Fibrosis refers to excessive build-up of scar tissue and extracellular matrix components in different organs. In recent years, it has been revealed that different cytokines and chemokines, especially Transforming growth factor beta (TGF-β) is involved in the pathogenesis of fibrosis. It has been shown that TGF-β is upregulated in fibrotic tissues, and contributes to fibrosis by mediating pathways that are related to matrix preservation and fibroblasts differentiation. There is no doubt that antioxidants protect against different inflammatory conditions by reversing the effects of nitrogen, oxygen and sulfur-based reactive elements. Oxidative stress has a direct impact on chronic inflammation, and as results, prolonged inflammation ultimately results in fibrosis. Different types of antioxidants, in the forms of vitamins, natural compounds or synthetic ones, have been proven to be beneficial in the protection against fibrotic conditions both in vitro and in vivo. In this study, we reviewed the role of different compounds with antioxidant activity in induction or inhibition of TGF-β/SMAD signalling pathway, with regard to different fibrotic conditions such as gastro-intestinal fibrosis, cardiac fibrosis, pulmonary fibrosis, skin fibrosis, renal fibrosis and also some rare cases of fibrosis, both in animal models and cell lines., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Gastrointestinal cancers are a huge worldwide health concern, which includes a wide variety of digestive tract cancers. Circular RNAs (circRNAs), a kind of non-coding RNA (ncRNAs), are a family of single-stranded, covalently closed RNAs that have become recognized as crucial gene expression regulators, having an impact on several cellular functions in cancer biology. The gut microbiome, which consists of several different bacteria, actively contributes to the regulation of host immunity, inflammation, and metabolism. CircRNAs and the gut microbiome interact significantly to greatly affect the growth of GI cancer. Several studies focus on the complex functions of circRNAs and the gut microbiota in GI cancers, including esophageal cancer, colorectal cancer, gastric cancer, hepatocellular cancer, and pancreatic cancer. It also emphasizes how changed circRNA expression profiles and gut microbiota affect pathways connected to malignancy as well as how circRNAs affect hallmarks of gastrointestinal cancers. Furthermore, circRNAs and gut microbiota have been recommended as biological markers for therapeutic targets as well as diagnostic and prognostic purposes. Targeting circRNAs and the gut microbiota for the treatment of gastrointestinal cancers is also being continued to study. Despite significant initiatives, the connection between circRNAs and the gut microbiota and the emergence of gastrointestinal cancers remains poorly understood. In this study, we will go over the most recent studies to emphasize the key roles of circRNAs and gut microbiota in gastrointestinal cancer progression and therapeutic options. In order to create effective therapies and plan for the future gastrointestinal therapy, it is important to comprehend the functions and mechanisms of circRNAs and the gut microbiota., (© 2023 The Authors.)

Background and Objectives: The resistance of Pseudomonas aeruginosa to antibiotics offers a significant challenge in the treatment of patients. This study aimed to investigate the antimicrobial resistance profile, biofilm-specific antimicrobial resistance genes, and genetic diversity of P. aeruginosa recovered from clinical samples., Materials and Methods: Totally 47 non-duplicate isolates of P. aeruginosa were recovered from various clinical samples. toxA, algD, ndvB, and tssC1 genes were detected in biofilm-producing isolates. The DNA sequences of the toxA and tssC1 genes were analyzed, by creating phylogenetic trees., Results: The findings revealed that 30 (63.8%) of the isolates tested positive for Extended spectrum β-lactamase (ESBL), whereas 31 (65.9%) tested positive for Metallo-β-lactamase (MBL) and all of the isolates presented the toxA genes, and 19.1%,17%, 6.3% presented by algD, ndvB and tssC1 genes. Besides, the phylogenetic trees of the toxA and tssC1 gene isolates suggested a genotype that was closely aligned with others. Gene sequencing similarity revealed 99% identity with other isolates deposited in GenBank., Conclusion: The occurrence of toxA was most prevalent. One isolate was recorded as a novel isolate in the global gene bank as a locally isolated strain from the city of Erbil that has never been identified in global isolates due to genetic variation., (Copyright © 2023 The Authors. Published by Tehran University of Medical Sciences.)

Lung cancer (LC) is the primary reason for cancer-associated fatalities globally. Due to both tumor-suppressing and tumor-promoting activities, the TGF-β family of growth factors is extremely essential to tumorigenesis. A non-coding single-stranded short RNA called microRNA (miRNA), which is made up of about 22 nt and is encoded by endogenous genes, can control normal and pathological pathways in various kinds of cancer, including LC. Recent research demonstrated that the TGF-β signaling directly can affect the synthesis of miRNAs through suppressor of mothers against decapentaplegic (SMAD)-dependent activity or other unidentified pathways, which could generate allostatic feedback as a result of TGF-β signaling stimulation and ultimately affect the destiny of cancer tissues. In this review, we emphasize the critical functions of miRNAs in lung cancer progression and, more critically, how they affect the TGF-β signaling pathway, and explore the role of both the TGF-β signaling pathway and miRNAs as potential therapeutic targets for improving the treatments of LC patients., Competing Interests: Declaration of competing interest The authors declare they have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

HAND2 antisense RNA 1 (HAND2-AS1) is a newly recognized lncRNA encoded by a gene on 4q34.1. This lncRNA has 10 exons and is predicted to have a positive effect on expression of certain genes. HAND2-AS1 is mainly considered as a tumor suppressive lncRNA in different tissues. Moreover, HAND2-AS1 has been shown to regulate expression of several targets with possible roles in the carcinogenesis through serving as a sponge for miRNAs. This lncRNA can also influence activity of BMP, TGF-β1, JAK/STAT and PI3K/Akt pathways. Down-regulation of HAND2-AS1 in tumor tissues has been associated with larger tumor size, higher tumor grade, higher chance of metastasis and poor clinical outcome. The present study aims at summarization of the impact of HAND2-AS1 in the carcinogenesis and its potential in cancer diagnosis or prediction of cancer prognosis., (© 2023. The Author(s).)

The cytokine known as transforming growth factor (TGF) is essential for cell development, differentiation, and apoptosis in BC. TGF-β dysregulation can either promote or inhibit tumor development, and it is a key signaling pathway in BC spread. A recently identified family of ncRNAs known as lncRNAs has received a great deal of effort and is an important regulator of many cellular processes, including transcription of genes, chromatin remodeling, progression of the cell cycle, and posttranscriptional processing. Furthermore, both TGF-β signaling and lncRNAs serve as important early-stage biomarkers for BC diagnosis and prognosis and also play a significant role in BC drug resistance. According to recent studies, lncRNAs can regulate TGF-β by modulating its cofactors in BC. However, the particular functions of lncRNAs and the TGF-β pathway in controlling BC progression are not well understood yet. This review explores the lncRNAs' functional properties in BC as tumor suppressors or oncogenes in the regulation of genes, with a focus on dysregulated TGF-β signaling. Further, we emphasize the functional roles of lncRNAs and TGF-β pathway in the progression of BC to discover new treatment strategies and better comprehend the fundamental cellular pathways., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Brain metastases in breast cancer (BC) patients are often associated with a poor prognosis. Recent studies have uncovered the critical roles of miRNAs in the initiation and progression of BC brain metastasis, highlighting the disease's underlying molecular pathways. miRNA-181c, miRNA-10b, and miRNA-21, for example, are all overexpressed in BC patients. It has been shown that these three miRNAs help tumors grow and metastasize by targeting genes that control how cells work. On the other hand, miRNA-26b5p, miRNA-7, and miRNA-1013p are all downregulated in BC brain metastasis patients. They act as tumor suppressors by controlling the expression of genes related to cell adhesion, angiogenesis, and invasion. Therapeutic miRNA targeting has considerable promise in treating BC brain metastases. Several strategies have been proposed to modulate miRNA expression, including miRNA-Mimics, antagomirs, and small molecule inhibitors of miRNA biogenesis. This review discusses the aberrant expression of miRNAs and metastatic pathways that lead to the spread of BC cells to the brain. It also explores miRNA therapeutic target molecular mechanisms and BC brain metastasis challenges with advanced strategies. The targeting of certain miRNAs opens a new door for the development of novel therapeutic approaches for this devastating disease., (© 2023 The Authors.)

Colorectal cancer (CRC) is ranked as the world's third-most prevalent cancer, and metastatic CRC considerably increases cancer-related fatalities globally. A number of complex mechanisms that are strictly controlled at the molecular level are involved in metastasis, which is the primary reason for death in people with CRC. Recently, it has become clear that exosomes, which are small extracellular vesicles released by non-tumorous and tumorigenic cells, play a critical role as communication mediators among tumor microenvironment (TME). To facilitate communication between the TME and cancer cells, non-coding RNAs (ncRNAs) play a crucial role and are recognized as potent regulators of gene expression and cellular processes, such as metastasis and drug resistance. NcRNAs are now recognized as potent regulators of gene expression and many hallmarks of cancer, including metastasis. Exosomal ncRNAs, like miRNAs, circRNAs, and lncRNAs, have been demonstrated to influence a number of cellular mechanisms that contribute to CRC metastasis. However, the molecular mechanisms that link exosomal ncRNAs with CRC metastasis are not well understood. This review highlights the essential roles that exosomal ncRNAs play in the progression of CRC metastatic disease and explores the therapeutic choices that are open to patients who have CRC metastases. However, exosomal ncRNA treatment strategy development is still in its early phases; consequently, additional investigation is required to improve delivery methods and find novel therapeutic targets as well as confirm the effectiveness and safety of these therapies in preclinical and clinical contexts., (© 2023 The Authors.)

MIR100HG is a long non-coding RNA (lncRNA) encoded by a locus on chr11:122,028,203-122,556,721. This gene can regulate cell proliferation, apoptosis, cell cycle transition and cell differentiation. MIR100HG was firstly identified through a transcriptome analysis and found to regulate differentiation of human neural stem cells. It is functionally related with a number of signalling pathways such as TGF-β, Wnt, Hippo and ERK/MAPK signalling pathways. Dysregulation of MIR100HG has been detected in a diversity of cancers in association with clinical outcomes. Moreover, it has a role in the pathophysiology of dilated cardiomyopathy, intervertebral disk degeneration and pulmonary fibrosis. The current study summarizes the role of these lncRNAs in human disorders., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Clustered regulatory interspaced short palindromic repeats (CRISPR) has changed biomedical research and provided entirely new models to analyze every aspect of biomedical sciences during the last decade. In the study of cancer, the CRISPR/CRISPR-associated protein (Cas) system opens new avenues into issues that were once unknown in our knowledge of the noncoding genome, tumor heterogeneity, and precision medicines. CRISPR/Cas-based gene-editing technology now allows for the precise and permanent targeting of mutations and provides an opportunity to target small non-coding RNAs such as microRNAs (miRNAs). However, the development of effective and safe cancer gene editing therapy is highly dependent on proper design to be innocuous to normal cells and prevent introducing other abnormalities. This study aims to highlight the cutting-edge approaches in cancer-gene editing therapy based on the CRISPR/Cas technology to target miRNAs in cancer therapy. Furthermore, we highlight the potential challenges in CRISPR/Cas-mediated miRNA gene editing and offer advanced strategies to overcome them., (© 2023. The Author(s).)

Toxic agents are broadly present in the environment, households, and workplaces. Contamination of food and drinking water with these agents results in entry of these materials to the body. The crosstalk between these agents and microRNAs (miRNAs) affects pathoetiology of several disorders. These agents can influence the redox status, release of inflammatory cytokines and mitochondrial function. Altered expression of miRNA is involved in the dysregulation of several pathophysiological conditions and signaling pathways. These molecules are also implicated in the adaption to environmental stimuli. Thus, the interactions between miRNAs and toxic materials might participate in the hazardous effects of these materials in the body. This review describes the effects of the toxic materials on miRNAs and the consequences of these interactions on the human health., Competing Interests: The authors declare they have no conflict of interest., (© 2023 The Authors.)

SIRT1 is a member of the sirtuin family functioning in the process of removal of acetyl groups from different proteins. This protein has several biological functions and is involved in the pathogenesis of metabolic diseases, malignancy, aging, neurodegenerative disorders and inflammation. Several long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs) have been found to interact with SIRT1. These interactions have been assessed in the contexts of sepsis, cardiomyopathy, heart failure, non-alcoholic fatty liver disease, chronic hepatitis, cardiac fibrosis, myocardial ischemia/reperfusion injury, diabetes, ischemic stroke, immune-related disorders and cancers. Notably, SIRT1-interacting non-coding RNAs have been found to interact with each other. Several circRNA/miRNA and lncRNA/miRNA pairs that interact with SIRT1 have been identified. These axes are potential targets for design of novel therapies for different disorders. In the current review, we summarize the interactions between three classes of non-coding RNAs and SIRT1., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ghafouri-Fard, Shoorei, Hussen, Poornajaf, Taheri and Sharifi.)

The long non-coding RNA (lncRNA) cancer susceptibility 11 (CASC11) is a newly identified lncRNA located on chromosome 8q24.21. The expression of lncRNA CASC11 has been found to be elevated in different cancer types and the prognosis of the tumor is inversely correlated with the high CASC11 expression. Moreover, lncRNA CASC11 has an oncogenic function in cancers. The biological characteristics of the tumors, such as proliferation, migration, invasion, autophagy, and apoptosis can be controlled by this lncRNA. In addition to interacting with miRNAs, proteins, transcription factors, and other molecules, the lncRNA CASC11 modulates signaling pathways including Wnt/β-catenin and epithelial-mesenchymal transition. In this review, we have summarized studies on the role of lncRNA CASC11 in the carcinogenesis from cell lines, in vivo , and clinical perspectives., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ghafouri-Fard, Harsij, Hussen, Taheri and Sharifi.)

Exosomes are an important group of extracellular vesicles that transfer several kinds of biomolecules and facilitate cell-cell communication. The content of exosomes, particularly the amounts of microRNA (miRNAs) inside these vesicles, demonstrates a disease-specific pattern reflecting pathogenic processes and may be employed as a diagnostic and prognostic marker. miRNAs may enter recipient cells through exosomes and generate a RISC complex that can cause degradation of the target mRNAs or block translation of their corresponding proteins. Therefore, exosome-derived miRNAs constitute an important mechanism of gene regulation in recipient cells. The miRNA content of exosomes can be used as an important tool in the detection of diverse disorders, particularly cancers. This research field has an important situation in cancer diagnosis. In addition, exosomal microRNAs offer a great deal of promise in the treatment of human disorders. However, there are still certain challenges to be resolved. The most important challenges are as follow: the detection of exosomal miRNAs should be standardized, exosomal miRNAs-associated studies should be conducted in large number of clinical samples, and experiment settings and detection criteria should be consistent across different labs. The goal of this article is to present an overview of the effects of exosome-derived microRNAs on a variety of diseases, including gastrointestinal, pulmonary, neurological, and cardiovascular diseases, with a particular emphasis on malignancies., Competing Interests: The authors declare they have no conflict of interest. Not applicable., (© 2023 The Authors.)

miRNA-93 is a member of the miR-106b-25 family and is encoded by a gene on chromosome 7q22.1. They play a role in the etiology of various diseases, including cancer, Parkinson's disease, hepatic injury, osteoarthritis, acute myocardial infarction, atherosclerosis, rheumatoid arthritis, and chronic kidney disease. Different studies have found that this miRNA has opposing roles in the context of cancer. Recently, miRNA-93 has been downregulated in breast cancer, gastric cancer, colorectal cancer, pancreatic cancer, bladder cancer, cervical cancer, and renal cancer. However, miRNA-93 is up-regulated in a wide variety of malignancies, such as lung, colorectal, glioma, prostate, osteosarcoma, and hepatocellular carcinoma. The aim of the current review is to provide an overview of miRNA-93's function in cancer disorder progression and non-cancer disorders, with a focus on dysregulated signaling pathways. We also give an overview of this miRNA's function as a biomarker of prognosis in cancer and emphasize how it contributes to drug resistance based on in vivo, in vitro, and human studies. Video Abstract., (© 2023. The Author(s).)

Long Intergenic Non-Protein Coding RNA 511 (LINC00511) is an RNA gene being mostly associated with lung cancer. Further assessments have shown dysregulation of this lncRNA in a variety of cancers. LINC00511 has interactions with hsa-miR-29b-3p, hsa-miR-765, hsa-mir-150, miR-1231, TFAP2A-AS2, hsa-miR-185-3p, hsa-miR-29b-1-5p, hsa-miR-29c-3p, RAD51-AS1 and EZH2. A number of transcription factors have been identified that regulate expression of LINC00511. The current narrative review summarizes the role of LINC00511 in different cancers with an especial focus on its prognostic impact in human cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ghafouri-Fard, Safarzadeh, Hussen, Taheri and Ayatollahi.)

Introduction: Contribution of MAPK14 in the pathogenesis of multiple sclerosis (MS) has been proposed by several studies. Long non-coding RNA (lncRNA) have been suggested to be functionally linked with Mitogen-activated protein kinase 14 (MAPK14)., Methods: Expression levels of MAPK14 and its associated lncRNAs were measured in the circulation of MS patients compared with control subjects., Results: Expression levels of NORAD and RAD51-AS1 were higher in total patients compared with controls (Expression ratio (95% CI) = 1.4 (1.04-1.89), P value = 0.015 and Expression ratio (95% CI) = 1.91 (1.43-2.6), P value = 0.0001, respectively). Conversely, ZNRD1ASP was under-expressed in cases compared with controls (Expression ratio (95% CI) = 0.61 (0.41-0.8), P value = 0.0005). In spite of the observed abnormal expression levels of these lncRNAs in the circulation of MS patients, their expressions were not correlated with Expanded Disability Status Scale (EDSS) score, disease duration or age at disease onset., Conclusion: To sum up, the current investigation shows dysregulation of MAPK14-related lncRNAs in MS patients., Competing Interests: The authors declare they have no conflict of interest., (© 2023 The Authors.)

Long non-coding RNAs (lncRNAs) are regulatory transcripts with essential roles in the pathogenesis of almost all types of cancers, including prostate cancer. They can act as either oncogenic lncRNAs or tumor suppressor ones in prostate cancer. Small nucleolar RNA host genes are among the mostly assessed oncogenic lncRNAs in this cancer. PCA3 is an example of oncogenic lncRNAs that has been approved as a diagnostic marker in prostate cancer. A number of well-known oncogenic lncRNAs in other cancers such as DANCR, MALAT1, CCAT1, PVT1, TUG1 and NEAT1 have also been shown to act as oncogenes in prostate cancer. On the other hand, LINC00893, LINC01679, MIR22HG, RP1-59D14.5, MAGI2-AS3, NXTAR, FGF14-AS2 and ADAMTS9-AS1 are among lncRNAs that act as tumor suppressors in prostate cancer. LncRNAs can contribute to the pathogenesis of prostate cancer via modulation of androgen receptor (AR) signaling, ubiquitin-proteasome degradation process of AR or other important signaling pathways. The current review summarizes the role of lncRNAs in the evolution of prostate cancer with an especial focus on their importance in design of novel biomarker panels and therapeutic targets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Taheri, Badrlou, Hussen, Kashi, Ghafouri-Fard and Baniahmad.)

Breast cancer is the most prevalent type of malignancy among women. Exosomes are extracellular vesicles of cell membrane origin that are released via exocytosis. Their cargo contains lipids, proteins, DNA, and different forms of RNA, including circular RNAs. Circular RNAs are new class of non-coding RNAs with a closed-loop shape involved in several types of cancer, including breast cancer. Exosomes contained a lot of circRNAs which are called exosomal circRNAs. By interfering with several biological pathways, exosomal circRNAs can have either a proliferative or suppressive role in cancer. The involvement of exosomal circRNAs in breast cancer has been studied with consideration to tumor development and progression as well as its effects on therapeutic resistance. However, its exact mechanism is still unclear, and there have not been available clinical implications of exo-circRNAs in breast cancer. Here, we highlight the role of exosomal circRNAs in breast cancer progression and to highlight the most recent development and potential of circRNAas therapeutic targets and diagnostics for breast cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hussen, Mohamadtahr, Abdullah, Hidayat, Rasul, Hama Faraj, Ghafouri-Fard, Taheri, Khayamzadeh and Jamali.)

Obsessive-compulsive disorder (OCD) is a disorder in which genetic factors participate. ANRIL is an example of long non-coding RNAs with crucial roles in the pathoetiology of multifactorial disorders, including neuropsychiatric conditions. We appraised association between rs1333045, rs1333048, rs10757278 and rs4977574 polymorphisms and OCD in Iranian population. There were no remarkable differences in allele and genotype distribution of rs1333045, rs1333048, rs4977574, and rs10757278 between OCD Patients and normal controls. However, the CCGG haplotype (equivalent to rs1333045, rs1333048, rs4977574 and rs10757278, respectively) has been shown to decrease risk of OCD (OR (95% CI) = 0.57 (0.39-0.85), P value-0.006 and FDR q-value = 0.041). On the other hand, TCGA haplotype has been found as a risk haplotype for OCD (OR (95% CI) = 5.17 (1.44-18.55), P value = 0.005 and FDR q-value = 0.041). In brief, the current study indicates association between two ANRIL haplotypes and risk of OCD in Iranian people., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Ferroptosis is a kind of cell death which has distinctive features differentiating it from autophagy, necrosis and apoptosis. This iron-dependent form of cell death is described by an increase in lipid reactive oxygen species, shrinkage of mitochondria and decrease in mitochondrial cristae. Ferroptosis is involved in the initiation and progression of many diseases and is regarded as a hotspot of investigations on treatment of disorders. Recent studies have shown that microRNAs partake in the regulation of ferroptosis. The impact of microRNAs on this process has been verified in different cancers as well as intervertebral disc degeneration, acute myocardial infarction, vascular disease, intracerebral hemorrhage, preeclampsia, hemorrhagic stroke, atrial fibrillation, pulmonary fibrosis and atherosclerosis. miR-675, miR-93, miR-27a, miR-34a and miR-141 have been shown to affect iron metabolism, antioxidant metabolism and lipid metabolism, thus influencing all pivotal mechanisms in the ferroptosis process. In the current review, we summarize the role of microRNAs in ferroptosis and their involvement in the pathetiology of malignant and non-malignant disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mahmoudi-Lamouki, Kadkhoda, Hussen and Ghafouri-Fard.)

LncRNA prostate androgen-regulated transcript 1 (PART1) is an important lncRNA in the carcinogenesis whose role has been firstly unraveled in prostate cancer. Expression of this lncRNA is activated by androgen in prostate cancer cells. In addition, this lncRNA has a role in the pathogenesis intervertebral disc degeneration, myocardial ischemia-reperfusion injury, osteoarthritis, osteoporosis and Parkinson's disease. Diagnostic role of PART1 has been assessed in some types of cancers. Moreover, dysregulation of PART1 expression is regarded as a prognostic factor in a variety of cancers. The current review provides a concise but comprehensive summary of the role of PART1 in different cancers and non-malignant disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ghafouri-Fard, Harsij, Hussen, Abdullah, Baniahmad, Taheri and Sharifi.)

Recent studies have shown dysregulation of several groups of long non-coding RNAs in the context of epilepsy. According to evidence regarding the role of regulatory T cells in this disorder, we examined expression levels of regulatory T cell-related lncRNAs, namely TH2-LCR, RMRP, IFNG-AS1 (NEST), MAFTRR and FLICR in the blood of epileptic cases compared with controls. Expression of RMRP was lower in patients with refractory epilepsy compared with controls [expression ratio (95% CI) = 0.32 (0.13-0.8), adjusted p -value = 0.0008]. Besides, its expression was lower in refractory patients vs. non-refractory patients [expression ratio (95% CI) = 0.2 (0.1-0.41), adjusted p -value < 0.0001]. Expression of TH2-LCR was lower in refractory patients vs. controls [expression ratio (95% CI) = 0.4 (0.17-0.93), adjusted p -value = 0.0044] and in refractory patients vs. non-refractory ones [Expression ratio = 0.28 (0.19-0.58), p -value < 0.0001]. Expression of NEST was higher in total patients [expression ratio (95% CI) = 2.48 (1.15-5.27), adjusted p -value = 0.0012] and in both groups of patients compared with controls. However, its expression was not different between refractory and non-refractory cases. Similarly, FLICR and MAFTRR were over-expressed in total cases and both groups of patients compared with controls, but their expressions were similar between refractory and non-refractory cases. MAFTRR could differentiate between total epileptic cases and controls with AUC value of 0.8. This lncRNA could separate refractory and non-refractory cases from healthy controls with AUC values of 0.73 and 0.88, respectively. This study provides evidence for deregulation of regulatory T cell-related lncRNAs in epilepsy and their potential role as diagnostic markers in this condition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sharifi, Eghtedarian, Taheri, Hussen, Eslami, Ghafouri-Fard and Sayad.)

Parkinson's disease (PD) is a distinctive clinical syndrome with several causes and clinical manifestations. Aside from an infectious cause, PD is a rapidly developing neurological disorder with a global rise in frequency. Notably, improved knowledge of molecular pathways and the developing novel diagnostic methods may result in better therapy for PD patients. In this regard, the amount of research on ceRNA axes is rising, highlighting the importance of these axes in PD. CeRNAs are transcripts that cross-regulate one another via competition for shared microRNAs (miRNAs). These transcripts may be either coding RNAs (mRNAs) or non-coding RNAs (ncRNAs). This research used a systematic review to assess validated loops of ceRNA in PD. The Prisma guideline was used to conduct this systematic review, which entailed systematically examining the articles of seven databases. Out of 309 entries, forty articles met all criteria for inclusion and were summarized in the appropriate table. CeRNA axes have been described through one of the shared vital components of the axes, including lncRNAs such as NEAT1, SNHG family, HOTAIR, MALAT1, XIST, circRNAs, and lincRNAs. Understanding the multiple aspects of this regulatory structure may aid in elucidating the unknown causal causes of PD and providing innovative molecular therapeutic targets and medical fields., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Asadi, Abed, Kouchakali, Fattahi, Sabaie, Moslehian, Sharifi-Bonab, Hussen, Taheri, Ghafouri-Fard and Rezazadeh.)

miR-20b is a microRNA with diverse and somehow contradictory roles in the pathogenesis of human disorders, especially cancers. It has been known to be a tumor suppressor in colon cancer, renal cell carcinoma, prostate cancer, osteosarcoma and papillary thyroid cancer. In lung cancer and breast cancers, both tumor suppressor and oncogenic effects have been identified for this miRNA. Finally, in T cell leukemia, hepatocellular carcinoma, esophageal squamous cell carcinoma and cervical and gastric cancers, miR-20b is regarded as an oncogenic miRNA. In several types of cancer, dysregulation of miR-20b has been recognized as a predictive marker for patients' survival. Dysregulation of miR-20b has also been recognized in Alzheimer's disease, diabetic retinopathy, myocardial ischemia/infarction, chronic hepatitis B and multiple sclerosis. In the current review, we have summarized the miR-20b targets and related cellular processes. We have also provided a review of participation of this miRNA in different human disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Khalilian, Abedinlou, Hussen, Imani and Ghafouri-Fard.)

Schizophrenia (SCZ) is a severe mental disorder with an unknown pathophysiology. Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin that has been associated with synapse plasticity, learning, and memory, as well as neurodevelopment and neuroprotection. The importance of neurodevelopmental and neurotoxicity-related components in the pathophysiology of SCZ has been highlighted in research on the neurobiology of this disease. The purpose of this research is to investigate the significant expression of two variables, tristetraprolin (TTP) and miR-16, which are known to be regulators of BDNF expression. Fifty Iranian Azeri SCZ patients were enrolled, and fifty healthy volunteers were age- and gender-matched as controls. A quantitative polymerase chain reaction measured the expression levels of the TTP and miR-16 in the peripheral blood (PB) of SCZ patients and healthy people. TTP expression levels in patients were higher than in controls, regardless of gender or age (posterior beta = 1.532, adjusted P-value = 0.012). TTP and miR-16 expression levels were found to be significantly correlated in both SCZ patients and healthy controls (r = 0.701, P < 0.001 and r = 0.777, P < 0.001, respectively). Due to the increased expression of TTP in SCZ and the existence of a significant correlation between TTP and miR-16, which helps to act on target mRNAs with AU-rich elements, this mechanism can be considered an influencing factor in SCZ., (© 2022. The Author(s).)

miR-671 is encoded by a gene on 7q36.1 and contributes to the pathogenesis of a variety of disorders, including diverse types of cancers, atherosclerosis, ischemic stroke, liver fibrosis, osteoarthritis, Parkinson's disease, rheumatoid arthritis, acute myocardial infarction and Crohn's disease. In the context of cancer, different studies have revealed opposite roles for this miRNA. In brief, it has been shown to be down-regulated in pancreatic ductal carcinoma, ovarian cancer, gastric cancer, osteosarcoma, esophageal squamous cell carcinoma and myelodysplastic syndromes. Yet, miR-671 has been up-regulated in glioma, colorectal cancer, prostate cancer and hepatocellular carcinoma. Studies in breast, lung and renal cell carcinoma have reported inconsistent results. The current review aims at summarization of the role of miR-671 in these disorders focusing on its target mRNA in each context and dysregulated signaling pathways. We also provide a summary of the role of this miRNA as a prognostic factor in malignancies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ghafouri-Fard, Askari, Hussen, Rasul, Hatamian, Taheri and Kiani.)

Bipolar disorder (BD) is a mental disorder that leads to abnormal swings in mood, energy, activity level, attention, and the capability to accomplish daily tasks. Several long non-coding RNAs (lncRNAs) are dysregulated in BD patients. We have compared expression levels of five NF-κB-associated lncRNAs, namely ANRIL, CEBPA-DT, H19, NKILA and HNF1A-AS1 in blood samples of BD patients compared with controls. While ANRIL, CEBPA-DT and HNF1-AS1 were significantly under-expressed in BD patients compared with controls, NKILA levels were higher in patients versus controls. Among differentially expressed genes, HFN1A-AS1 exhibited the best diagnostic parameters in the separation of patients from controls (AUC ± SD = 0.86 ± 0.03, sensitivity = 0.82, specificity = 0.82, P value < 0.0001). AUC values for NKILA, ANRIL and CEBPA-DT were 0.71, 0.68 and 0.65, respectively. In accordance with the previously reported participation of NF-ƙB in the pathophysiology of BD, the current study provides evidence for dysregulation of NF-κB-associated lncRNAs in BD., (© 2022. The Author(s).)

Suppressor of cytokine signalling (SOCS) family comprises a group of proteins that impede JAK/STAT signalling, thus being involved in the pathogenesis of immune-related conditions. In the present work, we aimed at identification of the role of SOCS genes in the pathogenesis of periodontitis through evaluation of their expression levels both in the circulation and in the affected tissues of patients. Thus, we measured expression levels of SOCS1-3 and SOCS5 transcripts in the blood and gingival samples of patients with periodontitis in comparison with control samples obtained during dental crown lengthening. Expressions of SOCS1, SOCS2, SOCS3 and SOCS5 genes were similar between gingival tissues of patients and controls. However, our results demonstrated under-expression of SOCS1 in blood samples of patients compared with controls (Ratio of mean expression (RME) = 0.47, P value = 0.04). The same pattern was observed among female subjects (RME = 0.38, P value = 0.04). SOCS2 was down-regulated in blood samples of female patients compared with female controls (RME = 0.22, P value = 0.04). SOCS3 was also under-expressed in the circulation of total cases versus total controls (RME = 0.29, P value = 0.02) and in female patients compared with female controls (RME = 0.19, P value = 0.04). Expression of SOCS5 was not different between blood samples two study groups. SOCS2 had the best function in separation of affected tissues from unaffected ones (AUC = 0.66, sensitivity = 0.39, specificity = 0.83). SOCS3 was superior to other transcripts in differentiation of blood samples of patients from normal blood samples (AUC = 0.69, sensitivity = 0.81, specificity = 0.68). Combination of transcript levels of SOCS1, SOCS2, SOCS3 and SOCS5 genes enhanced the AUC values to 0.64 and 0.67 in tissue and blood specimens, respectively. Taken together, certain SOCS genes have been found to be dysregulated in the circulation of patients with periodontitis., (© 2022. The Author(s).)

Membrane vesicles having a diameter of 30-150 nm are known as exosomes. Several cancer types secrete exosomes, which may contain proteins, circular RNAs (circRNAs), microRNAs, or DNA. CircRNAs are endogenous RNAs that do not code for proteins and can create continuous and covalently closed loops. In cancer pathogenesis, especially metastasis, exosomal circRNAs (exo-circRNAs) have a crucial role mainly due to the frequently aberrant expression levels within tumors. However, neither the activities nor the regulatory mechanisms of exo-circRNAs in advancing lung cancer (LC) are obvious. A better understanding of the regulation and network connections of exo-circRNAs will lead to better treatment for LCs. The main objective of the current review is to highlight the functions and mechanisms of exo-circRNAs in LC and assess the relationships between exo-circRNA dysregulation and LC progression. In addition, underline the possible therapeutic targets based on exo-circRNA modulating., (© 2022. The Author(s).)

The construction of a competing endogenous RNA (ceRNA) network is an important step in the identification of the role of differentially expressed genes in cancers. In the current research, we used a number of bioinformatics tools to construct the ceRNA network in prostate cancer and identify the importance of these modules in predicting the survival of patients with this type of cancer. An assessment of microarray data of prostate cancer and normal samples using the Limma package led to the identification of differential expressed (DE) RNAs that we stratified into mRNA, lncRNA, and miRNAs, resulting in 684 DEmRNAs, including 437 downregulated DEmRNAs (such as TGM4 and SCGB1A1) and 241 upregulated DEmRNAs (such as TDRD1 and CRISP3); 6 DElncRNAs, including 1 downregulated DElncRNA (H19) and 5 upregulated DElncRNAs (such as PCA3 and PCGEM1); and 59 DEmiRNAs, including 30 downregulated DEmiRNAs (such as hsa-miR-1274a and hsa-miR-1274b) and 29 upregulated DEmiRNAs (such as hsa-miR-1268 and hsa-miR-1207-5p). The ceRNA network contained a total of 5 miRNAs, 5 lncRNAs, and 17 mRNAs. We identified hsa-miR-17, hsa-miR-93, hsa-miR-150, hsa-miR-25, PART1, hsa-miR-125b, PCA3, H19, RND3, and ITGB8 as the 10 hub genes in the ceRNA network. According to the ROC analysis, the expression levels of 19 hub genes showed a high diagnostic value. Taken together, we introduce a number of novel promising diagnostic biomarkers for prostate cancer.

Long non-coding RNAs are demonstrated to contribute to carcinogenesis. TMPO Antisense RNA 1 (TMPO-AS1) is an example of lncRNAs with crucial roles in this process. This lncRNA serves as a sponge for miR-320a, miR-383-5p, miR-329-3p, miR-126, miR-329, miR-199a-5p, miR-577, miR-4731-5p, miR-140-5p, miR-1179, miR-143-3p, miR-326, miR-383-5p, let-7c-5p, let-7g-5p, miR-199a-5p, miR-200c, miR-204-3p, miR-126-5p, miR-383-5p, miR-498, miR-143-3p, miR-98-5p, miR-140 and miR-143. It can also affect activity of PI3K/Akt/mTOR pathway. The current review summarizes the role of TMPO-AS1 in the carcinogenesis and assessment of its potential as a marker for certain types of cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ghafouri-Fard, Askari, Hussen, Taheri and Mokhtari.)

Long Intergenic Non-Protein Coding RNA 665 (LINC00665) is an RNA gene located on the minus strand of chromosome 19. This lncRNA acts as a competing endogenous RNA for miR-4458, miR-379-5p, miR-551b-5p, miR-3619-5p, miR-424-5p, miR-9-5p, miR-214-3p, miR-126-5p, miR-149-3p, miR-379-5p, miR-665, miR-34a-5p, miR-186-5p, miR-138-5p, miR-181c-5p, miR-98, miR-195-5p, miR-224-5p, miR-3619, miR-708, miR-101, miR-1224-5p, miR-34a-5p, and miR-142-5p. Via influencing expression of these miRNAs, it can enhance expression of a number of oncogenes. Moreover, LINC00665 can influence activity of Wnt/β-Catenin, TGF-β, MAPK1, NF-κB, ERK, and PI3K/AKT signaling. Function of this lncRNA has been assessed through gain-of-function tests and/or loss-of-function studies. Furthermore, diverse research groups have evaluated its expression levels in tissue samples using microarray and RT-qPCR techniques. In this manuscript, we have summarized the results of these studies and categorized them in three sections, i.e., cell line studies, animal studies, and investigations in clinical samples.

miR-16-5p is microRNA with important roles in the development of diverse malignancies including neuroblastoma, osteosarcoma, hepatocellular carcinoma, cervical cancer, breast cancer, brain tumors, gastrointestinal cancers, lung cancer and bladder cancer. This miRNA has 22 nucleotides. hsa-miR-16-5p is produced by MIR16-1 gene. First evidence for its participation in the carcinogenesis has been obtained by studies reporting deletion and/or down-regulation of these miRNAs in chronic lymphocytic leukemia. Subsequent studies have shown down-regulation of miR-16-5p in a variety of cancer cell lines and clinical samples. Besides, tumor suppressor role of miR-16-5p has been verified in animal models of different types of cancers. Studies in these models have shown that over-expression of this miRNA or modulation of expression of lncRNAs that sponge this miRNA can block carcinogenic processes. In the current review, we summarize function of miR-16-5p in the development and progression of different cancers., (© 2022. The Author(s).)

Schizophrenia (SCZ) is a serious mental condition with an unknown cause. According to the reports, Brodmann Area 10 (BA10) is linked to the pathology and cortical dysfunction of SCZ, which demonstrates a number of replicated findings related to research on SCZ and the dysfunction in tasks requiring cognitive control in particular. Genetics' role in the pathophysiology of SCZ is still unclear. Therefore, it may be helpful to understand the effects of these changes on the onset and progression of SCZ to find novel mechanisms involved in the regulation of gene transcription. In order to determine the molecular regulatory mechanisms affecting the SCZ, the long non-coding RNA (lncRNA)-associated competing endogenous RNAs (ceRNAs) axes in the BA10 area were determined using a bioinformatics approach in the present work. A microarray dataset (GSE17612) consisted of brain post-mortem tissues of the BA10 area from SCZ patients and matched healthy subjects was downloaded from the Gene Expression Omnibus (GEO) database. This dataset included probes for both lncRNAs and mRNAs. Using the R software's limma package, the differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were found. The RNA interactions were also discovered using the DIANA-LncBase and miRTarBase databases. In the ceRNA network, positive correlations between DEmRNAs and DElncRNAs were evaluated using the Pearson correlation coefficient. Finally, lncRNA-associated ceRNA axes were built by using the co-expression and DElncRNA-miRNA-DEmRNA connections. We identified the DElncRNA-miRNA-DEmRNA axes, which included two key lncRNAs ( PEG3-AS1, MIR570HG ), seven key miRNAs ( hsa-miR-124-3p , hsa-miR-17-5p, hsa-miR-181a-5p, hsa-miR-191-5p, hsa-miR-26a-5p, hsa-miR-29a-3p, hsa-miR-29b-3p ), and eight key mRNAs ( EGR1, ETV1, DUSP6, PLOD2, CD93, SERPINB9, ANGPTL4, TGFB2 ). Furthermore, DEmRNAs were found to be enriched in the "AGE-RAGE signaling pathway in diabetic complications", "Amoebiasis", "Transcriptional misregulation in cancer", "Human T-cell leukemia virus 1 infection", and "MAPK signaling pathway". This study offers research targets for examining significant molecular pathways connected to the pathogenesis of SCZ, even though the function of these ceRNA axes still needs to be investigated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sabaie, Gholipour, Asadi, Abed, Sharifi-Bonab, Taheri, Hussen, Brand, Neishabouri and Rezazadeh.)

Programmed death-ligand 1 (PD-L1) is a transmembrane protein with essential roles in the suppression of adaptive immune responses. As an immune checkpoint molecule, PD-L1 can be exploited by cancer cells to evade the anti-tumor attacks initiated by the immune system. Thus, blockade of the PD1/PD-L1 axis can eliminate the suppressive signals and release the antitumor immune responses. Identification of the underlying mechanisms of modulation of the activity of the PD1/PD-L1 axis would facilitate the design of more efficacious therapeutic options and better assignment of patients for each option. Recent studies have confirmed the interactions between miRNAs/lncRNAs/circ-RNAs and the PD1/PD-L1 axis. In the current review, we give a summary of interactions between these transcripts and PD-L1 in the context of cancer. We also overview the consequences of these interactions in the determination of the response of patients to anti-cancer drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ghafouri-Fard, Shoorei, Hussen, Poornajaf, Taheri and Sharifi.)

The Cyclin-dependent kinase (CDK) class of serine/threonine kinases has crucial roles in the regulation of cell cycle transition and is mainly involved in the pathogenesis of cancers. The expression of CDKs is controlled by a complex regulatory network comprised of genetic and epigenetic mechanisms, which are dysregulated during the progression of cancer. The abnormal activation of CDKs results in uncontrolled cancer cell proliferation and the induction of cancer stem cell characteristics. The levels of CDKs can be utilized to predict the prognosis and treatment response of cancer patients, and further understanding of the function and underlying mechanisms of CDKs in human tumors would pave the way for future cancer therapies that effectively target CDKs. Defects in the regulation of cell cycle and mutations in the genes coding cell-cycle regulatory proteins lead to unrestrained proliferation of cells leading to formation of tumors. A number of treatment modalities have been designed to combat dysregulation of cell cycle through affecting expression or activity of CDKs. However, effective application of these methods in the clinical settings requires recognition of the role of CDKs in the progression of each type of cancer, their partners, their interactions with signaling pathways and the effects of suppression of these kinases on malignant features. Thus, we designed this literature search to summarize these findings at cellular level, as well as in vivo and clinical levels., (© 2022. The Author(s).)

Exosomes are naturally occurring nanosized particles that aid intercellular communication by transmitting biological information between cells. Exosomes have therapeutic efficacy that can transfer their contents between cells as natural carriers. In addition, the exosomal contents delivered to the recipient pathological cells significantly inhibit cancer progression. However, exosome-based tumor treatments are inadequately precise or successful, and various challenges should be adequately overcome. Here, we discuss the significant challenges that exosomes face as drug carriers used for therapeutic targets and strategies for overcoming these challenges in order to promote this new incoming drug carrier further and improve future clinical outcomes. We also present techniques for overcoming these challenges., (© 2022. The Author(s).)

Long non-coding RNAs (lncRNAs) have been identified as modulators of gastric carcinogenesis. Evaluation of expression amounts of these transcripts is a primary but essential step for recognition of the role of lncRNAs in the carcinogenesis. Therefore, we compared expressions of LINC-ROR , HOXA-AS2 , MEG3 and HOTTIP lncRNAs in gastric cancer samples and nearby non-cancerous samples. Expression levels of LINC-ROR , HOXA-AS2 and MEG3 lncRNAs have been lower in gastric cancer samples compared with nearby non-cancerous samples (Expression ratios = 0.26, 0.37 and 0.36; P values = 0.021, 0.015 and 0.032, respectively). However, expression levels of HOTTIP were not significantly different between gastric cancer tissues and nearby tissues (P value = 0.43). HOTTIP expression was associated with tumor size (P value = 0.04). In addition, MEG3 expression was associated with site of primary tumor (P = 0.0003). Expressions of LINC-ROR and HOXA-AS2 were not associated with any clinical or pathological parameter. ROC curve analysis revealed that HOXA-AS2 and LINC-ROR could significantly differentiate between gastric cancer samples and nearby non-cancerous tissues (AUC values = 0.68 and 0.64; P values = 0.01 and 0.04, respectively). Taken together, the current investigation provides clues for contribution of LINC-ROR , HOXA-AS2 and MEG3 lncRNAs in gastric carcinogenesis and warrants further mechanistical assays., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Slow-burning inflammation at the lesion rim is connected to the expansion of chronic multiple sclerosis (MS) lesions. However, the underlying processes causing expansion are not clearly realized. In this context, the current study used a bioinformatics approach to identify the expression profiles and related lncRNA-associated ceRNA regulatory axes in the periplaque region in MS patients. Expression data (GSE52139) from periplaque regions in the secondary progressive MS spinal cord and controls were downloaded from the Gene Expression Omnibus database (GEO), which has details on mRNAs and lncRNAs. Using the R software's limma package, the differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were found. The RNA interactions were also found using the DIANA-LncBase, miRTarBase, and HMDD databases. The Pearson correlation coefficient was used to determine whether there were any positive correlations between DEmRNAs and DElncRNAs in the ceRNA network. Finally, lncRNA-associated ceRNA axes were created based on co-expression and connections between DElncRNA, miRNA, and DEmRNA. We used the Enrichr tool to enrich the biological process, molecular function, and pathways for DEmRNAs and DElncRNAs. A network of DEmRNAs' protein-protein interactions was developed, and the top five hub genes were found using Cytoscape and STRING. The current study indicates that 15 DEmRNAs, including FOS , GJA1 , NTRK2 , CTNND1 , and SP3 , are connected to the MS ceRNA network. Additionally, four DElncRNAs (such as TUG1 , ASB16-AS1 , and LINC01094 ) that regulated the aforementioned mRNAs by sponging 14 MS-related miRNAs (e.g., hsa-miR-145-5p , hsa-miR-200a-3p , hsa-miR-20a-5p , hsa-miR-22-3p , hsa-miR-23a-3p , hsa-miR-27a-3p , hsa-miR-29b-3p , hsa-miR-29c-3p , hsa-miR-34a-5p ) were found. In addition, the analysis of pathway enrichment revealed that DEmRNAs were enriched in the pathways for the "MAPK signaling pathway", "Kaposi sarcoma-associated herpesvirus infection", "Human immunodeficiency virus one infection", "Lipid and atherosclerosis", and "Amphetamine addiction". Even though the function of these ceRNA axes needs to be investigated further, this study provides research targets for studying ceRNA-mediated molecular mechanisms related to periplaque demyelination in MS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sabaie, Khorami Rouz, Kouchakali, Heydarzadeh, Asadi, Sharifi-Bonab, Hussen, Taheri, Ayatollahi and Rezazadeh.)

LINC00467 is an example of long intergenic non-coding RNAs whose roles in human disorders are being identified. This gene coding LINC00467 is located on chromosome 1: 211,382,736 - 211,435,570 forward strand. This lncRNA has been firstly recognized through a microarray-based lncRNA profiling as an N-Myc target in neuroblastoma cells. Further studies have shown up-regulation of LINC00467 in different cancer including those originated from brain, gastrointestinal tract, lung and breast. It acts as a molecular sponge for miR-339, miR-138-5p, miR-107, miR-133b, miR-451a, miR-485-5p, miR-7-5p, miR-485-5p, miR-339-3p, miR-200a, miR-1285-3p, miR-299-5p, miR-509-3p, miR-18a-5p, miR-9-5p and miR-20b-5p. LINC00467 can regulate activity of NF-κB, STAT1, Wnt/b-catenin, Akt and ERK1/2 signaling pathways. Accumulating evidence indicates oncogenic role of LINC00467. The current review article aims at providing an overview of LINC00467 in the carcinogenesis., (© 2022. The Author(s).)