Sarcopenia and noncoding RNAs: A comprehensive review.

Sarcopenia is an elderly disease and is related to frailty and loss of muscle mass (atrophy) of older adults. The exact molecular mechanisms contributing to the pathogenesis of disease are yet to be discovered. In recent years, the role of noncoding RNAs in the pathogenesis of almost every kind of malignant and nonmalignant conditions is pinpointed. Regarding their regulatory function, there have been an increased number of studies on the role of noncoding RNAs in the progress of sarcopenia. In this manuscript, we review the role of microRNAs and long noncoding RNAs in development and progression of disease. We also discuss their potential as therapeutic targets in this condition.

Identification of key differentially expressed genes in SARS-CoV-2 using RNA-seq analysis with a systems biology approach.

COVID-19 is associated with dysregulation of several genes and signaling pathways. Based on the importance of expression profiling in identification of the pathogenesis of COVID-19 and proposing novel therapies for this disorder, we have employed an in silico approach to find differentially expressed genes between COVID-19 patients and healthy controls and their relevance with cellular functions and signaling pathways. We obtained 630 DEmRNAs, including 486 down-regulated DEGs (such as CCL3 and RSAD2) and 144 up-regulated DEGs (such as RHO and IQCA1L), and 15 DElncRNAs, including 9 down-regulated DElncRNAs (such as PELATON and LINC01506) and 6 up-regulated DElncRNAs (such as AJUBA-DT and FALEC). The PPI network of DEGs showed the presence of a number immune-related genes such as those coding for HLA molecules and interferon regulatory factors. Taken together, these results highlight the importance of immune-related genes and pathways in the pathogenesis of COVID-19 and suggest novel targets for treatment of this disorder.

New Potential MicroRNA Biomarkers in Human Immunodeficiency Virus Elite Controllers, Human Immunodeficiency Virus Infections, and Coinfections with Hepatitis B Virus or Hepatitis C Virus.

INTRODUCTION: This research aimed to evaluate the specific microRNA (miRNA) including miR-17-5p, miRN-140-3p miR-191-5p, miR-200c-3p, and miR-N367 and cellular factors (p21, SDF-1, XCL1, CCL-2, and IL-2) in controlling replication of human immunodeficiency virus (HIV) in ECs. METHODS: The expression of miRNAs was assessed between healthy control groups and patient groups including ART-naïve HIV, HIV ART, ECs, and coinfection (HIV-HBV and HIV-HCV) via real-time PCR technique. Besides, the expression level of the nef gene and cellular factors were assessed by the ELISA method. The differences in the level of cellular factors and selected miRNAs between study groups were analyzed using the Kruskal-Wallis H or one-way ANOVA test. In addition, the potential of selected miRNAs as biomarkers for discriminating study groups was assessed by the receiver-operator characteristic (ROC) curve analysis. RESULTS: Some miRNAs in ECs, HIV ART, and healthy controls have similar expression patterns, whereas a miRNA expression profile of patient groups significantly differed compared to EC and control groups. According to ROC curve analyses, the miR-17-5p, miR-140-3p miR-191-5p, miR-200c-3p, and miR-N367 can be served as biomarkers for discriminating ECs from ART-naïve HIV-infected groups. There was a significant correlation between some miRNAs and cellular factors/the viral load as well. CONCLUSION: This report demonstrated a differentiation in the expression of selected immunological factors and cellular/viral miRNAs in ECs compared to other patient groups. Some miRNAs and cellular factors are involved in the viral replication control, immune response/modulation and can be used as biomarkers for diagnosis of ECs and differentiation with other groups. Differential expression of these miRNAs and cellular factors in different stages of HIV infection can help in finding novel ways for infection control.

SMAD4 contributes to chondrocyte and osteocyte development.

Different cellular and molecular mechanisms contribute to chondrocyte and osteocyte development. Although vital roles of the mothers against decapentaplegic homolog 4 (also called 'SMAD4') have been discussed in different cancers and stem cell-related studies, there are a few reviews summarizing the roles of this protein in the skeletal development and bone homeostasis. In order to fill this gap, we discuss the critical roles of SMAD4 in the skeletal development. To this end, we review the different signalling pathways and also how SMAD4 defines stem cell features. We also elaborate how the epigenetic factors-ie DNA methylation, histone modifications and noncoding RNAs-make a contribution to the chondrocyte and osteocyte development. To better grasp the important roles of SMAD4 in the cartilage and bone development, we also review the genotype-phenotype correlation in animal models. This review helps us to understand the importance of the SMAD4 in the chondrocyte and bone development and the potential applications for therapeutic goals.

Non-coding RNA-associated competitive endogenous RNA regulatory networks: Novel diagnostic and therapeutic opportunities for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), as the most prevalent liver malignancy, is annually diagnosed in more than half a million people worldwide. HCC is strongly associated with hepatitis B and C viral infections as well as alcohol abuse. Obesity and nonalcoholic fatty liver disease (NAFLD) also significantly enhance the risk of liver cancer. Despite recent improvements in therapeutic approaches, patients diagnosed in advanced stages show poor prognosis. Accumulating evidence provides support for the regulatory role of non-coding RNAs (ncRNAs) in cancer. There are a variety of reports indicating the regulatory role of microRNAs (miRNAs) in different stages of HCC. Long non-coding RNAs (LncRNAs) exert their effects by sponging miRNAs and controlling the expression of miRNA-targeted genes. Circular RNAs (circRNAs) perform their biological functions by acting as transcriptional regulators, miRNA sponges and protein templates. Diverse studies have illustrated that dysregulation of competing endogenous RNA networks (ceRNETs) is remarkably correlated with HCC-causing diseases such as chronic viral infections, nonalcoholic steatohepatitis and liver fibrosis/cirrhosis. The aim of the current article was to provide an overview of the role and molecular mechanisms underlying the function of ceRNETs that modulate the characteristics of HCC such as uncontrolled cell proliferation, resistance to cell death, metabolic reprogramming, immune escape, angiogenesis and metastasis. The current knowledge highlights the potential of these regulatory RNA molecules as novel diagnostic biomarkers and therapeutic targets in HCC.

Identification of a six-microRNA signature as a potential diagnostic biomarker in breast cancer tissues.

BACKGROUND: Breast cancer (BC) is by far the most common malignancy among women. Epigenetic modulators, microRNAs in particular, may set stages for BC development and its progression. Herein, we aimed to assess the diagnostic potentiality of a signature of six miRNAs (i.e., hsa-miR-25-3p, -29a-5p, -105-3p, -181b1-5p, -335-5p, and -339-5p) in BC and adjacent non-tumor tissues. METHODS: A pair of 50 tumor and adjacent non-tumor samples were taken from BC patients. The expression of each candidate miRNA was measured using quantitative reverse transcription PCR. To investigate the possible roles of each miRNA and their impressions on BC prognosis, in silico tools were used. Receiver operating characteristic (ROC) curves were performed to determine the diagnostic accuracy of each miRNA and the possible association of their expression with clinicopathological characteristics was analyzed. RESULTS: Our findings showed the upregulation of hsa-miR-25-3p, -29a-5p, -105-3p, and -181b1-5p, and the downregulation of hsa-miR-335-5p and -339-5p in BC tumor compared to corresponding adjacent tissues. Except for hsa-miR-339-5p, the up-/down-regulation of the candidate miRNAs was associated with TNM stages. Except for hsa-miR-105-3p, each candidate miRNA was correlated with HER-2 status. ROC curve analysis showed that the signature of six-miRNA is a potential biomarker distinguishing between tumor and non-tumor breast tissue samples. CONCLUSION: We showed that the dysregulation of a novel signature of six-miRNA can be used as a potential biomarker for BC diagnosis.

A review on the importance of miRNA-135 in human diseases.

MicroRNA-135 (miR-135) is a microRNA which is involved in the pathoetiology of several neoplastic and non-neoplastic conditions. Both tumor suppressor and oncogenic roles have been reported for this miRNA. Studies in prostate, renal, gallbladder and nasopharyngeal cancers as well as glioma have shown down-regulation of miR-135 in cancerous tissues compared with controls. These studies have also shown the impact of miR-135 down-regulation on enhancement of cell proliferation and aggressive behavior. Meanwhile, miR-135 has been shown to be up-regulated in bladder, oral, colorectal and liver cancers. Studies in breast, gastric, lung and pancreatic cancers as well as head and neck squamous cell carcinoma have reported dual roles for miR-135. Dysregulation of miR-135 has also been noted in various non-neoplastic conditions such as Alzheimer's disease, atherosclerosis, depression, diabetes, Parkinson, pulmonary arterial hypertension, nephrotic syndrome, endometriosis, epilepsy and allergic conditions. In the current review, we summarize the role of miR-135 in the carcinogenesis as well as development of other disorders.

The role of miRNAs and lncRNAs in conferring resistance to doxorubicin.

Doxorubicin is a chemotherapeutic agent that inhibits topoisomerase II, intercalates within DNA base pairs and results in oxidative DNA damage, thus inducing cell apoptosis. Although it is effective in the treatment of a wide range of human cancers, the emergence of resistance to this drug can increase tumour growth and impact patients' survival. Numerous molecular mechanisms and signalling pathways have been identified that induce resistance to doxorubicin via stimulation of cell proliferation, cell cycle switch and preclusion of apoptosis. A number of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have also been identified that alter sensitivity to doxorubicin. Understanding the particular impact of these non-coding RNAs in conferring resistance to doxorubicin has considerable potential to improve selection of chemotherapeutic regimens for cancer patients. Moreover, modulation of expression of these transcripts is a putative strategy for combating resistance. In the current paper, the influence of miRNAs and lncRNAs in the modification of resistance to doxorubicin is discussed.

Emerging role of non-coding RNAs in the course of HIV infection.

Recent studies have shown that non-coding region of the human genome can exert important regulatory roles on critical biological functions, including response to viral infections, among them is human immunodeficiency virus (HIV). HIV/AIDS is characterized by a gradual diminution of CD4 + T cells resulting in progressive deterioration of host immune responses and eventually high vulnerability to opportunistic infections and cancer. T cells functions have been shown to be delicately regulated by an active functional network of non-coding RNAs. Several lncRNAs such as MALAT1, NEAT1, GAS5, LOC102549805, NKILA, BACE1-AS, LINC00313, RP11-539L10.2, PVT1, LINC00173, NRON and AK130181 have been found to affect response of immune system to HIV or its pathological consequences. Moreover, numerous miRNAs such as hsa-miR-191-5p, miR-155, miR-103, miR-107, miR-150, miR-144, miR-125b, miR-146a, miR-146b-5p and miR-15a are involved in this process. In the current manuscript, we explain the role of lncRNAs and miRNAs in the regulation of response to HIV infection, apoptosis and activity of T cells, reactivation or latency of this virus and even pathological manifestations such as Tat-mediated induction of astrocytic amyloidosis.

In silico characterization of competing endogenous RNA network in glioblastoma multiforme with a systems biology approach.

Glioblastoma multiforme (GBM) is the most frequent malignant type of primary brain cancers and is a malignancy with poor prognosis. Thus, it is necessary to find novel therapeutic modalities based on molecular events occur at different stages of tumor progression. We used expression profiles of GBM tissues that contained long non-coding RNA (lncRNA), microRNA (miRNA) and mRNA signatures to make putative ceRNA networks. Our strategy led to identification of 1080 DEmRNAs, including 777 downregulated DEmRNAs (such as GJB6 and SLC12A5) and 303 upregulated DEmRNAs (such as TOP2A and RRM2), 19 DElncRNAs, including 16 downregulated DElncRNAs (such as MIR7-3HG and MIR124-2HG) and 3 upregulated DElncRNAs (such as CRNDE and XIST) and 49 DEmiRNAs, including 10 downregulated DEmiRNAs (such as hsa-miR-10b-5p and hsa-miR-1290) and 39 upregulated DEmiRNAs (such as hsa-miR-219a-2-3p and hsa-miR-338-5p). We also identified DGCR5, MIAT, hsa-miR-129-5p, XIST, hsa-miR-128-3p, PART1, hsa-miR-10b-5p, LY86-AS1, CRNDE, and DLX6-AS1 as 10 hub genes in the ceRNA network. The current study provides novel insight into molecular events during GBM pathogenesis. The identified molecules can be used as therapeutic targets for GBM.

Assessment of expression of oxytocin-related lncRNAs in schizophrenia.

BACKGROUND: Schizophrenia is a neuropsychiatric disorder characterized by a variety of clinical manifestations. This disorder has a complex inheritance. Oxytocinegic system has been shown to be implicated in the pathophysiology of schizophrenia. This system can alter social cognition through direct interaction with dopaminergic signaling, facilitating brain-stimulation reward, reduction of defense mechanism and stress reactivity, and modulation of social information processing through enhancing the greatness of social incentives. Long non-coding RNAs (lncRNAs) can affect activity of oxytocinegic system, thus contributing in the etiology of this disorder. METHODS: We designed the current study to appraise dysregulation of nine oxytocin-associated mRNAs and lncRNAs in the venous blood of patients with schizophrenia. RESULTS: Expression of FOS was up-regulated in total patients compared with total control group (Expression ratio (95% CI)= 13.64 (5.46-34.05), adjusted P value<0.0001) and in female patients compared with female control group (Expression ratio (95% CI)=32.13 (5.81-176), adjusted P value<0.0001). Such pattern was also seen for Lnc-FOXF1 (Expression ratio (95% CI)= 6.41 (2.84-14.3), adjusted P value<0.0001 and Expression ratio (95% CI)= 14.41 (3.2-64.44), adjusted P value<0.0001, respectively). ITPR1 was down-regulated in total patients compared with total controls (Expression ratio (95% CI)= 0.22 (0.076-0.67), adjusted P value=0.0079). ROC curve analyses demonstrated that FOS had the best AUC value among other genes in differentiation between patients and controls (AUC=0.78). CONCLUSION: The above-mentioned results imply dysregulation of oxytocin-related genes in the circulatory blood of patients with schizophrenia.

Strategies to overcome the side effects of chimeric antigen receptor T cell therapy.

Chimeric antigen receptor (CAR) therapy is a method directing T lymphocytes against antigens on the surface of tumors, increasing target cell elimination. Genetic engineering enhances the capability of immune cells to detect new antigens expressed on cell surfaces. CAR T cell therapy is a significant breakthrough for treating human malignancies; however, different side effects (e.g., cytokine release syndrome) restrict its application. Improving design and using various combined receptors enhance the performance of these cells. This review discusses limitations and risk factors associated with CAR T cell therapy. We also review some alternative approaches for developing the next generation of CAR T cells.

The Emerging Role of Non-Coding RNAs in Osteoarthritis.

Osteoarthritis (OS) is the most frequent degenerative condition in the joints, disabling many adults. Several abnormalities in the articular cartilage, subchondral bone, synovial tissue, and meniscus have been detected in the course of OA. Destruction of articular cartilage, the formation of osteophytes, subchondral sclerosis, and hyperplasia of synovial tissue are hallmarks of OA. More recently, several investigations have underscored the regulatory roles of non-coding RNAs (ncRNAs) in OA development. Different classes of non-coding RNAs, including long ncRNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), have been reported to affect the development of OA. The expression level of these transcripts has also been used as diagnostic tools in OA. In the present article, we aimed at reporting the role of these transcripts in this process. We need to give a specific angle on the pathology to provide meaningful thoughts on it.

An updated review of the role of lncRNAs and their contribution in various molecular subtypes of breast cancer.

Introduction: Breast cancer (BC) is the most significant threat to women's life. To demonstrate its molecular mechanisms, which results in BC progression, it is crucial to develop approaches to enhance prognosis and survival in BC cases.Areas covered: In the current study, we aimed to highlight the updated data on the oncogenic and tumor suppressive roles of lncRNAs in the progression of various subtypes of BC by specifically putting importance on the functional characteristics, modulatory agents, therapeutic potential, future perspectives and challenges of lncRNAs in BC. We reviewed recent studies published between 2019 and 2020.Expert opinion: The latest investigations have demonstrated that the long non-coding RNAs (lncRNAs) participate in different BC molecular subtypes via different molecular mechanisms; however, the exact functional information of the lncRNAs has yet to be elucidated. The studied lncRNAs could be more applicable as therapeutic targets in BC treatment after pre-clinical and clinical studies.

Exploring the interaction of quercetin-3-O-sophoroside with SARS-CoV-2 main proteins by theoretical studies: A probable prelude to control some variants of coronavirus including Delta.

The aim of this study was to investigate the mechanism of interaction between quercetin-3-O-sophoroside and different SARS-CoV-2's proteins which can bring some useful details about the control of different variants of coronavirus including the recent case, Delta. The chemical structure of the quercetin-3-O-sophoroside was first optimized. Docking studies were performed by CoV disease-2019 (COVID-19) Docking Server. Afterwards, the molecular dynamic study was done using High Throughput Molecular Dynamics (HTMD) tool. The results showed a remarkable stability of the quercetin-3-O-sophoroside based on the calculated parameters. Docking outcomes revealed that the highest affinity of quercetin-3-O-sophoroside was related to the RdRp with RNA. Molecular dynamic studies showed that the target E protein tends to be destabilized in the presence of quercetin-3-O-sophoroside. Based on these results, quercetin-3-O-sophoroside can show promising inhibitory effects on the binding site of the different receptors and may be considered as effective inhibitor of the entry and proliferation of the SARS-CoV-2 and its different variants. Finally, it should be noted, although this paper does not directly deal with the exploring the interaction of main proteins of SARS-CoV-2 Delta variant with quercetin-3-O-sophoroside, at the time of writing, no direct theoretical investigation was reported on the interaction of ligands with the main proteins of Delta variant. Therefore, the present data may provide useful information for designing some theoretical studies in the future for studying the control of SARS-CoV-2 variants due to possible structural similarity between proteins of different variants.