Identification of miR-125a and miR-106b signature as a potential diagnostic biomarker in breast cancer tissues.

MicroRNAs (miRNAs) have essential roles in the etiology of breast cancer and are regarded as possible markers in this malignancy. In order to find new markers for breast cancer, the current study has measured expression level of four miRNAs, namely miR-125a, miR-106b, miR-96 and miR-92a-3p in the paired breast samples. Expression levels of miR-125a and miR-106b were higher in tumoral tissues compared with control tissues (Expression ratios (95% CI) = 4.01 (1.96-8.19) and 3.9 (1.95-7.81); P values = 0.0005 and 0.0003, respectively). miR-106b and miR-125a differentiated between malignant and non-malignant tissues with AUC values of 0.7 and 0.67, respectively. We detected association between expression of miR-106b and clinical stage (P = 0.03), in a way that its expression was the lowest in the advanced stages. Finally, significant relationships were found between miR-96 and miR-125a in both tumoral and non-tumoral specimens (ρ = 0.76 and 0.69, respectively). This nonparametric measure of rank correlation also showed relationship between miR-106b and miR-96 in both sets of samples (ρ = 0.63 and 0.61, respectively). Cumulatively, the assessed miRNAs, particularly miR-125a and miR-106b are putative targets for further expression and functional assays in breast cancer.

Advanced approaches of the use of circRNAs as a replacement for cancer therapy.

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.

Alteration in the expression of long non-coding RNAs in the circulation of migraineurs.

BACKGROUND: Current studies have shown emerging roles of lncRNAs in the pathobiology of neuropathic pain and migraine. METHODS: We have chosen five lncRNAs, namely, PVT1, DSCAM-AS, MEG3, LINC-ROR, and SPRY4-IT1 for assessment of their expression in the circulation of migraineurs. RESULTS: Expressions of PVT1 and MEG3 were higher in total migraineurs and both subgroups compared with controls (P < 0.0001). Meanwhile, expression of both lncRNA was higher in migraineurs with aura versus migraineurs without aura (P value < 0.0001 and = 0.01, respectively). Expression of DSCAM-AS1 was not different between any groups of patients compared with controls. Expression of LINC-ROR was elevated in total patients and patients with aura compared with controls (P value = 0.0002 and < 0.0001, respectively). It was also over-expressed in migraineurs with aura vs. migraineurs without aura (P = 0.01). Finally, expression of SPRY4-IT1 was higher in total patients and patients without aura compared with migraine-free persons (P values < 0.0001). Expressions of five mentioned lncRNAs were correlated in almost all study groups. In patients without aura, correlations were significant only for two pairs (SPRY4-IT1/PVT1 and SPRY4-IT1/DSCAM-AS1). PVT1 and MEG3 had the appropriate AUC, sensitivity and specificity values for separation of total migraineurs and both groups of patients from controls. The highest AUC value was reported for PVT1 in separation of migraineurs with aura from healthy controls (AUC = 0.98). CONCLUSION: Cumulatively, our study shows evidence for deregulation of lncRNAs in migraineurs.

Mesenchymal stromal cells (MSCs) as a therapeutic agent of inflammatory disease and infectious COVID-19 virus: live or dead mesenchymal?

The COVID-19 infection is a worldwide disease that causes numerous immune-inflammatory disorders, tissue damage, and lung dysfunction. COVID-19 vaccines, including those from Pfizer, AstraZeneca, and Sinopharm, are available globally as effective interventions for combating the disease. The severity of COVID-19 can be most effectively reduced by mesenchymal stromal cells (MSCs) because they possess anti-inflammatory activity and can reverse lung dysfunction. MSCs can be harvested from various sources, such as adipose tissue, bone marrow, peripheral blood, inner organs, and neonatal tissues. The regulation of inflammatory cytokines is crucial in inhibiting inflammatory diseases and promoting the presence of anti-inflammatory cytokines for infectious diseases. MSCs have been employed as therapeutic agents for tissue damage, diabetes, autoimmune diseases, and COVID-19 patients. Our research aimed to determine whether live or dead MSCs are more suitable for the treatment of COVID-19 patients. Our findings concluded that dead MSCs, when directly administered to the patient, offer advantages over viable MSCs due to their extended presence and higher levels of immune regulation, such as T-reg, B-reg, and IL-10, compared to live MSCs. Additionally, dead and apoptotic MSCs are likely to be more readily captured by monocytes and macrophages, prolonging their presence compared to live MSCs.

Role of miR-424 in the carcinogenesis

Recent studies have revealed the impact of microRNAs (miRNAs) in the carcinogenic process. miR-424 is a miRNA whose role in this process is being to be identified. Experiments in the ovarian cancer, cervical cancer, hepatocellular carcinoma, neuroblastoma, breast cancer, osteosarcoma, intrahepatic cholangiocarcinoma, prostate cancer, endometrial cancer, non-small cell lung cancer, hemangioma and gastric cancer have reported down-regulation of miR-424. On the other hand, this miRNA has been found to be up-regulated in melanoma, laryngeal and esophageal squamous cell carcinomas, glioma, multiple myeloma and thyroid cancer. Expression of this miRNA is regulated by methylation status of its promoter. Besides, LINC00641, CCAT2, PVT1, LIN00657, LINC00511 and NNT-AS1 are among lncRNAs that act as molecular sponges for miR-424, thus regulating its expression. Moreover, several members of SNHG family of lncRNAs have been found to regulate expression of miR-424. This miRNA is also involved in the regulation of E2F transcription factors. The current review aims at summarization of the role of miR-424 in the process of cancer evolution and its impact on clinical outcome of patients in order to find appropriate markers for malignancies (AU)

Role of circular RNAs and gut microbiome in gastrointestinal cancers and therapeutic targets.

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.

A review on the role of FOXD2-AS1 in human disorders.

FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) is a long non-coding RNA being transcribed from a locus on chromosome 1p33. This transcript has been found to be up-regulated in tumor samples of almost all types of malignancies in association with a significant increase in malignant features. FOXD2-AS1 can affect activity of PI3K/AKT, AKT/mTOR, Hippo/YAP, Notch, NRf2, Wnt/ß-catenin, NF-ƙB and ERK/MAPK pathways. Furthermore, it can enhance stem cell properties in cancer cells and prompt epithelial-mesenchymal transition. It is also involved in induction of resistance to a variety of anticancer agents such as adriamycin, cisplatin, 5-fluorouracil, temozolomide and gemcitabine. This article summarizes the impact of FOXD2-AS1 in diverse human disorders.

Role of miR-424 in the carcinogenesis.

Recent studies have revealed the impact of microRNAs (miRNAs) in the carcinogenic process. miR-424 is a miRNA whose role in this process is being to be identified. Experiments in the ovarian cancer, cervical cancer, hepatocellular carcinoma, neuroblastoma, breast cancer, osteosarcoma, intrahepatic cholangiocarcinoma, prostate cancer, endometrial cancer, non-small cell lung cancer, hemangioma and gastric cancer have reported down-regulation of miR-424. On the other hand, this miRNA has been found to be up-regulated in melanoma, laryngeal and esophageal squamous cell carcinomas, glioma, multiple myeloma and thyroid cancer. Expression of this miRNA is regulated by methylation status of its promoter. Besides, LINC00641, CCAT2, PVT1, LIN00657, LINC00511 and NNT-AS1 are among lncRNAs that act as molecular sponges for miR-424, thus regulating its expression. Moreover, several members of SNHG family of lncRNAs have been found to regulate expression of miR-424. This miRNA is also involved in the regulation of E2F transcription factors. The current review aims at summarization of the role of miR-424 in the process of cancer evolution and its impact on clinical outcome of patients in order to find appropriate markers for malignancies.

Antioxidant therapy against TGF-ß/SMAD pathway involved in organ fibrosis.

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-ß) is involved in the pathogenesis of fibrosis. It has been shown that TGF-ß 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-ß/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.

Diverse functions of miR-328 in the carcinogenesis.

MicroRNA-328 (miR-328) is an RNA gene that is primarily associated with lung cancer, and its encoding gene is located on 16q22.1. Expression of miR-328 has been observed in lung and esophagus tissues based on RNAseq data. Although several studies have aimed at the detection of miR-328 levels in tumor tissues, there is an obvious discrepancy between the results of these studies. Even in a certain type of cancer, some studies have reported up-regulation of miR-328 in cancerous tissues versus control tissues, while others have reported its down-regulation. This discrepancy might be attributed to different stages/grades of tumor tissues or other clinical characteristics. This review article focuses on the available literature to explore the functions of miR-328 in the development of human carcinogenesis.

LncRNA SNHG12: A budding star in human diseases.

Small nucleolar RNA host gene 12 (SNHG12) is a long non-coding RNA (lncRNA) that contributes in a variety of human pathologies. This lncRNAs acts as molecular sponge for various miRNAs, namely miR-200c-5p, miR-129-5p, miR-30a-3p, miR-195, miR-133b, miR-199a/b-5p, miR-320b, miR-16, miR-15a, miR-218-5p, miR-320 and a number of other miRNAs. Through this mechanism, SNHG12 can affect activity of HIF-1α, Wnt/ß-catenin, VEGF, PI3K/AKT/mTOR, PTEN, NF-κB and ERK-1/2 signaling. SNHG12 can affect pathogenesis of several disorders, including those arising from genitourinary, gastrointestinal, pulmonary, central nervous and cardiovascular systems. These effects have been best characterized in the context of cancer where it can be used as a possible diagnostic and prognostic marker. In order to summarize the role of this lncRNA in human disorders, particularly cancer and highlight its potential application in biomedical studies, we designed the current review. We also emphasized on its diagnostic and prognostic roles.

New insights of miRNA molecular mechanisms in breast cancer brain metastasis and therapeutic targets.

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.

Current landscape of miRNAs and TGF-ß signaling in lung cancer progression and therapeutic targets.

Lung cancer (LC) is the primary reason for cancer-associated fatalities globally. Due to both tumor-suppressing and tumor-promoting activities, the TGF-ß 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-ß 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-ß 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-ß signaling pathway, and explore the role of both the TGF-ß signaling pathway and miRNAs as potential therapeutic targets for improving the treatments of LC patients.

Exosomal non-coding RNAs: Blueprint in colorectal cancer metastasis and therapeutic targets.

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.

Role of long non-coding RNAs and TGF-ß signaling in the regulation of breast cancer pathogenesis and therapeutic targets.

The cytokine known as transforming growth factor (TGF) is essential for cell development, differentiation, and apoptosis in BC. TGF-ß 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-ß 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-ß by modulating its cofactors in BC. However, the particular functions of lncRNAs and the TGF-ß 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-ß signaling. Further, we emphasize the functional roles of lncRNAs and TGF-ß pathway in the progression of BC to discover new treatment strategies and better comprehend the fundamental cellular pathways.

Nanoparticle-mediated delivery of microRNAs-based therapies for treatment of disorders.

miRNAs represent appropriate candidates for treatment of several disorders. However, safe and efficient delivery of these small-sized transcripts has been challenging. Nanoparticle-based delivery of miRNAs has been used for treatment of a variety of disorders, particularly cancers as well as ischemic stroke and pulmonary fibrosis. The wide range application of this type of therapy is based on the important roles of miRNAs in the regulation of cell behavior in physiological and pathological conditions. Besides, the ability of miRNAs to inhibit or increase expression of several genes gives them the superiority over mRNA or siRNA-based therapies. Preparation of nanoparticles for miRNA delivery is mainly achieved through using protocols originally developed for drugs or other types of biomolecules. In brief, nanoparticle-based delivery of miRNAs is regarded as a solution for overcoming all challenges in the therapeutic application of miRNAs. Herein, we provide an overview of studies which used nanoparticles as delivery systems for facilitation of miRNAs entry into target cells for the therapeutic purposes. However, our knowledge about miRNA-loaded nanoparticles is limited, and it is expected that numerous therapeutic possibilities will be revealed for miRNA-loaded nanoparticles in future.

Interaction between SIRT1 and non-coding RNAs in different disorders.

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.

Targeting miRNA by CRISPR/Cas in cancer: advantages and challenges.

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.

In silico identification of potential miRNAs -mRNA inflammatory networks implicated in the pathogenesis of COVID-19.

COVID-19 has been found to affect the expression profile of several mRNAs and miRNAs, leading to dysregulation of a number of signaling pathways, particularly those related to inflammatory responses. In the current study, a systematic biology procedure was used for the analysis of high-throughput expression data from blood specimens of COVID-19 and healthy individuals. Differentially expressed miRNAs in blood specimens of COVID-19 vs. healthy specimens were then identified to construct and analyze miRNA-mRNA networks and predict key miRNAs and genes in inflammatory pathways. Our results showed that 171 miRNAs were expressed as outliers in box plot and located in the critical areas according to our statistical analysis. Among them, 8 miRNAs, namely miR-1275, miR-4429, miR-4489, miR-6721-5p, miR-5010-5p, miR-7110-5p, miR-6804-5p and miR-6881-3p were found to affect expression of key genes in NF-KB, JAK/STAT and MAPK signaling pathways implicated in COVID-19 pathogenesis. In addition, our results predicted that 25 genes involved in above-mentioned inflammatory pathways were targeted not only by these 8 miRNAs but also by other obtained miRNAs (163 miRNAs). The results of the current in silico study represent candidate targets for further studies in COVID-19.

Expression analysis of cytoskeleton regulator RNA and Cyclin Dependent Kinase Inhibitor 2B genes in breast cancer.

BACKGROUND: Breast cancer has been found to be associated with deregulation of several non-coding genes and mRNA coding genes. OBJECTIVE: To assess expressions of CYTOR and CDKN2B in breast cancer and adjacent samples and find their relevance with clinical data. METHODS: We enumerated expression level of CDKN2B and CYTOR in 43 newly diagnosed breast cancer samples and their adjacent specimens using real-time PCR method Expression data was judged using Wilcoxon matched-pairs signed rank test. RESULTS: CYTOR level was higher in tumors compared with adjacent tissues. Nevertheless, there was no difference in expression of CDKN2B between these two sets of tissues. ROC curve analysis showed that CYTOR levels can differentiate between tumoral and adjacent tissues with AUC, specificity and sensitivity values of 0.65, 37% and 92% (P= 0.017). There was a positive correlation between expression levels of CYTOR and CDKN2B genes in breast cancer tissues (r= 0.5 and P= 0.0008) as well as adjacent tissues (r= 0.79 and P< 0.0001). Relative expression level of CDKN2B in normal tissues was associated with clinical stage (P= 0.014). Moreover, relative expression level of CDKN2B in tumor tissues was associated with the body weight. There was no other association between expressions of CYTOR and CDKN2B and clinical or pathological variables. CONCLUSIONS: Cumulatively, this study offers evidence for involvement of these genes in the pathoetiology of breast cancer.