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1.
Life Sci ; 352: 122850, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38901687

ABSTRACT

AIMS: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Nicotinamide phosphoribosyl-transferase (NAMPT) was found to be over-expressed in several cancers including CRC. NAMPT-Antisense (NAMPT-AS) is a novel long non-coding RNA (lncRNA) recently reported to be associated with triple negative breast cancer. However, its role in CRC has not been investigated. This study was designed to explore the role of lncRNA NAMPT-AS in CRC, and to investigate its circulating serum exosomal levels in subjects with/without CRC. MAIN METHODS: We analyzed CRC patients' data in The Cancer Genome Atlas (TCGA). LncRNA NAMPT-AS and NAMPT mRNA levels were measured in serum exosomes isolated from CRC patients and healthy control subjects and were also measured in CRC-tissues using qRT-PCR. Serum NAMPT protein levels were measured by ELISA, and immunohistochemical analyses were done for NAMPT and Ki67 in CRC tissues. KEY FINDINGS: Serum exosomal NAMPT-AS levels were found to be significantly higher in CRC patients compared to control subjects and significantly positively correlated with serum exosomal NAMPT mRNA and circulating NAMPT protein. Tissue NAMPT-AS was found to be significantly positively associated with tissue and serum exosomal NAMPT levels. Higher serum exosomal NAMPT-AS levels were found to be associated with higher susceptibility for CRC. Gene-ontology results and survival analysis of TCGA-data showed a potential classification of CRC samples based on NAMPT-AS levels and association of NAMPT-AS upregulation with poor CRC prognosis and survival. SIGNIFICANCE: These results portray NAMPT-AS as a novel potential diagnostic/prognostic biomarker and key molecular mediator in CRC.

2.
Curr Atheroscler Rep ; 26(8): 395-410, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38869707

ABSTRACT

PURPOSE OF REVIEW: To eradicate atherosclerotic diseases, novel biomarkers, and future therapy targets must reveal the burden of early atherosclerosis (AS), which occurs before life-threatening unstable plaques form. The chemical and biological features of microRNAs (miRNAs) make them interesting biomarkers for numerous diseases. We summarized the latest research on miRNA regulatory mechanisms in AS progression studies, which may help us use miRNAs as biomarkers and treatments for difficult-to-treat diseases. RECENT FINDINGS: Recent research has demonstrated that miRNAs have a regulatory function in the observed changes in gene and protein expression during atherogenesis, the process that leads to atherosclerosis. Several miRNAs play a role in the development of atherosclerosis, and these miRNAs could potentially serve as non-invasive biomarkers for atherosclerosis in various regions of the body. These miRNAs have the potential to serve as biomarkers and targets for early treatment of atherosclerosis. The start and development of AS require different miRNAs. It reviews new research on miRNAs affecting endothelium, vascular smooth muscle, vascular inflammation, lipid retention, and cholesterol metabolism in AS. A miRNA gene expression profile circulates with AS everywhere. AS therapies include lipid metabolism, inflammation reduction, and oxidative stress inhibition. Clinical use of miRNAs requires tremendous progress. We think tiny miRNAs can enable personalized treatment.


Subject(s)
Atherosclerosis , Biomarkers , MicroRNAs , Humans , Atherosclerosis/genetics , Atherosclerosis/metabolism , Atherosclerosis/diagnosis , Atherosclerosis/therapy , MicroRNAs/genetics , MicroRNAs/metabolism , Biomarkers/metabolism , Prognosis , Animals
3.
Pathol Res Pract ; 254: 155147, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38246033

ABSTRACT

Asthma is a diverse inflammatory illness affecting the respiratory passages, leading to breathing challenges, bouts of coughing and wheezing, and, in severe instances, significant deterioration in quality of life. Epigenetic regulation, which involves the control of gene expression through processes such as post-transcriptional modulation of microRNAs (miRNAs), plays a role in the evolution of various asthma subtypes. In immune-mediated diseases, miRNAs play a regulatory role in the behavior of cells that form the airway structure and those responsible for defense mechanisms in the bronchi and lungs. They control various cellular processes such as survival, growth, proliferation, and the production of chemokines and immune mediators. miRNAs possess chemical and biological characteristics that qualify them as suitable biomarkers for diseases. They allow for the categorization of patients to optimize drug selection, thus streamlining clinical management and decreasing both the economic burden and the necessity for critical care related to the disease. This study provides a concise overview of the functions of miRNAs in asthma and elucidates their regulatory effects on the underlying processes of the disease. We provide a detailed account of the present status of miRNAs as biomarkers for categorizing asthma, identifying specific asthma subtypes, and selecting appropriate treatment options.


Subject(s)
Asthma , MicroRNAs , Humans , MicroRNAs/genetics , MicroRNAs/therapeutic use , Epigenesis, Genetic , Quality of Life , Asthma/diagnosis , Asthma/genetics , Asthma/drug therapy , Biomarkers
4.
Pathol Res Pract ; 253: 155007, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38061270

ABSTRACT

Alzheimer's disease (AD) is a multifaceted, advancing neurodegenerative illness that is responsible for most cases of neurological impairment and dementia in the aged population. As the disease progresses, affected individuals may experience cognitive decline, linguistic problems, affective instability, and behavioral changes. The intricate nature of AD reflects the altered molecular mechanisms participating in the affected human brain. MicroRNAs (miRNAs, miR) are essential for the intricate control of gene expression in neurobiology. miRNAs exert their influence by modulating the transcriptome of brain cells, which typically exhibit substantial genetic activity, encompassing gene transcription and mRNA production. Presently, comprehensive studies are being conducted on AD to identify miRNA-based signatures that are indicative of the disease pathophysiology. These findings can contribute to the advancement of our understanding of the mechanisms underlying this disorder and can inform the development of therapeutic interventions based on miRNA and related RNA molecules. Therefore, this comprehensive review provides a detailed holistic analysis of the latest advances discussing the emerging role of miRNAs in the progression of AD and their possible application as potential biomarkers and targets for therapeutic interventions in future studies.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , MicroRNAs , Humans , Aged , MicroRNAs/genetics , MicroRNAs/metabolism , Alzheimer Disease/diagnosis , Alzheimer Disease/genetics , Alzheimer Disease/therapy , Brain/metabolism , RNA, Messenger , Biomarkers/metabolism
5.
Pathol Res Pract ; 253: 155027, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38101159

ABSTRACT

Oral cancer (OC) is a widely observed neoplasm on a global scale. Over time, there has been an increase in both its fatality and incidence rates. Oral cancer metastasis is a complex process that involves a number of cellular mechanisms, including invasion, migration, proliferation, and escaping from malignant tissue through either lymphatic or vascular channels. MicroRNAs (miRNAs) are a crucial class of short non-coding RNAs recognized as significant modulators of diverse cellular processes and exert a pivotal influence on the carcinogenesis pathway, functioning either as tumor suppressors or as oncogenes. It has been shown that microRNAs (miRNAs) have a role in metastasis at several stages, including epithelial-mesenchymal transition, migration, invasion, and colonization. This regulation is achieved by targeting key genes involved in these pathways by miRNAs. This paper aims to give a contemporary analysis of OC, focusing on its molecular genetics. The current literature and emerging advancements in miRNA dysregulation in OC are thoroughly examined. This project would advance OC diagnosis, prognosis, therapy, and therapeutic implications.


Subject(s)
MicroRNAs , Mouth Neoplasms , Humans , MicroRNAs/metabolism , Carcinogenesis/genetics , Mouth Neoplasms/diagnosis , Mouth Neoplasms/genetics , Oncogenes , Drug Resistance, Neoplasm/genetics , Gene Expression Regulation, Neoplastic/genetics , Epithelial-Mesenchymal Transition/genetics
6.
Pathol Res Pract ; 252: 154947, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37977032

ABSTRACT

Malignant pleural mesothelioma (MPM) is a highly invasive form of lung cancer that adversely affects the pleural and other linings of the lungs. MPM is a very aggressive tumor that often has an advanced stage at diagnosis and a bad prognosis (between 7 and 12 months). When people who have been exposed to asbestos experience pleural effusion and pain that is not explained, MPM should be suspected. After being diagnosed, most MPM patients have a one- to four-year life expectancy. The life expectancy is approximately six months without treatment. Despite the plethora of current molecular investigations, a definitive universal molecular signature has yet to be discovered as the causative factor for the pathogenesis of MPM. MicroRNAs (miRNAs) are known to play a crucial role in the regulation of gene expression at the posttranscriptional level. The association between the expression of these short, non-coding RNAs and several neoplasms, including MPM, has been observed. Although the incidence of MPM is very low, there has been a significant increase in research focused on miRNAs in the past few years. In addition, miRNAs have been found to have a role in various regulatory signaling pathways associated with MPM, such as the Notch signaling network, Wnt/ß-catenin, mutation of KRAS, JAK/STAT signaling circuit, protein kinase B (AKT), and Hedgehog signaling pathway. This study provides a comprehensive overview of the existing understanding of the roles of miRNAs in the underlying mechanisms of pathogenic symptoms in MPM, highlighting their potential as viable targets for therapeutic interventions.


Subject(s)
Lung Neoplasms , Mesothelioma, Malignant , Mesothelioma , MicroRNAs , Pleural Neoplasms , Humans , MicroRNAs/genetics , Mesothelioma/diagnosis , Pleural Neoplasms/pathology , Hedgehog Proteins , Lung Neoplasms/pathology , Signal Transduction/genetics
7.
Pathol Res Pract ; 250: 154817, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37713736

ABSTRACT

Malignant pleural mesothelioma (MPM) is a highly lethal form of pleural cancer characterized by a scarcity of effective therapeutic interventions, resulting in unfavorable prognoses for afflicted individuals. Besides, many patients experience substantial consequences from being diagnosed in advanced stages. The available diagnostic, prognostic, and therapeutic options for MPM are restricted in scope. MicroRNAs (miRNAs) are a subset of small, noncoding RNA molecules that exert significant regulatory influence over several cellular processes within cell biology. A wide range of miRNAs have atypical expression patterns in cancer, serving specific functions as either tumor suppressors or oncomiRs. This review aims to collate, epitomize, and analyze the latest scholarly investigations on miRNAs that are believed to be implicated in the dysregulation leading to MPM. miRNAs are also discussed concerning their potential clinical usefulness as diagnostic and prognostic biomarkers for MPM. The future holds promising prospects for enhancing diagnostic, prognostic, and therapeutic modalities for MPM, with miRNAs emerging as a potential trigger for such advancements.

8.
Pathol Res Pract ; 249: 154771, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37611429

ABSTRACT

Merkel cell carcinoma (MCC) is an uncommon invasive form of skin cancer that typically manifests as a nodule on the face, head, or neck that is flesh-colored or bluish-red in appearance. Rapid growth and metastasis are hallmarks of MCC. MCC has the second-greatest mortality rate among skin cancers after melanoma. Despite the recent cascade of molecular investigations, no universal molecular signature has been identified as responsible for MCC's pathogenesis. The microRNAs (miRNAs) play a critical role in the post-transcriptional regulation of gene expression. Variations in the expression of these short, non-coding RNAs have been associated with various malignancies, including MCC. Although the incidence of MCC is very low, a significant amount of study has focused on the interaction of miRNAs in MCC. As such, the current survey is a speedy intensive route revealing the potential involvement of miRNAs in the pathogenesis of MCC beyond their association with survival in MCC.


Subject(s)
Carcinoma, Merkel Cell , Melanoma , MicroRNAs , Skin Neoplasms , Humans , MicroRNAs/genetics , Carcinoma, Merkel Cell/genetics , Signal Transduction , Skin Neoplasms/genetics , Melanoma/genetics
9.
Pathol Res Pract ; 249: 154763, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37595447

ABSTRACT

Merkel cell carcinoma (MCC) is a rare, aggressive form of skin malignancy with a high recurrence commonly within two to three years of initial diagnosis. The incidence of MCC has nearly doubled in the past few decades. Options for diagnosing, assessing, and treating MCC are limited. MicroRNAs (miRNAs) are a class of small, non-coding RNA molecules that play an important role in controlling many different aspects of cell biology. Many miRNAs are aberrantly expressed in distinct types of cancer, with some serving as tumor suppressors and others as oncomiRs. Therefore, the future holds great promise for the utilization of miRNAs in enhancing diagnostic, prognostic, and therapeutic approaches for MCC. Accordingly, the goal of this article is to compile, summarize, and discuss the latest research on miRNAs in MCC, highlighting their potential clinical utility as diagnostic and prognostic biomarkers.


Subject(s)
Carcinoma, Merkel Cell , MicroRNAs , Skin Neoplasms , Humans , MicroRNAs/genetics , Carcinoma, Merkel Cell/diagnosis , Carcinoma, Merkel Cell/genetics , Prognosis , Skin Neoplasms/diagnosis , Skin Neoplasms/genetics
10.
Pathol Res Pract ; 248: 154690, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37473498

ABSTRACT

Adrenocortical carcinoma (ACC) is a highly malignant infrequent tumor with a dismal prognosis. microRNAs (miRNAs, miRs) are crucial in post-transcriptional gene expression regulation. Due to their ability to regulate multiple gene networks, miRNAs are central to the hallmarks of cancer, including sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, replicative immortality, induction/access to the vasculature, activation of invasion and metastasis, reprogramming of cellular metabolism, and avoidance of immune destruction. ACC represents a singular form of neoplasia associated with aberrations in the expression of evolutionarily conserved short, non-coding RNAs. Recently, the role of miRNAs in ACC has been examined extensively despite the disease's rarity. Hence, the current review is a fast-intensive track elucidating the potential role of miRNAs in the pathogenesis of ACC besides their association with the survival of ACC.


Subject(s)
Adrenal Cortex Neoplasms , Adrenocortical Carcinoma , MicroRNAs , Humans , Adrenocortical Carcinoma/genetics , Adrenocortical Carcinoma/pathology , MicroRNAs/genetics , MicroRNAs/metabolism , Adrenal Cortex Neoplasms/genetics , Adrenal Cortex Neoplasms/pathology , Prognosis , Signal Transduction/genetics
11.
Pathol Res Pract ; 248: 154682, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37451195

ABSTRACT

microRNAs (also known as miRNAs or miRs) are a class of small non-coding RNAs that play a critical role in post-transcriptional gene regulation as negative gene regulators by binding complementary sequences in the 3'-UTR of target messenger RNAs (mRNAs) leading to translational repression and/or target degradation a wide range of genes and biological processes, including cell proliferation, invasion, migration, and apoptosis. The development and progression of cancer have been linked to the anomalous expression of miRNAs. According to recent studies, miRNAs have been found to regulate the expression of cancer-related genes through multiple signaling pathways in gallbladder cancer (GBC). Besides, miRNAs are implicated in several modulatory signaling pathways of GBC, including the Notch signaling pathway, JAK/STAT signaling pathway, protein kinase B (AKT), and Hedgehog signaling pathway. This review summarizes our current knowledge of the functions of miRNAs in the mechanisms underlying the pathogenic symptoms of GBC and illustrates their potential significance as treatment targets.


Subject(s)
Carcinoma in Situ , Gallbladder Neoplasms , MicroRNAs , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Gallbladder Neoplasms/pathology , Hedgehog Proteins/genetics , Gene Expression Regulation , Signal Transduction/genetics , RNA, Messenger/genetics
12.
Pathol Res Pract ; 248: 154665, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37418996

ABSTRACT

Adrenocortical carcinoma (ACC) is an uncommon aggressive endocrine malignancy that is nonetheless associated with significant mortality and morbidity rates because of endocrine and oncological consequences. Recent genome-wide investigations of ACC have advanced our understanding of the disease, but substantial obstacles remain to overcome regarding diagnosis and prognosis. MicroRNAs (miRNAs, miRs) play a crucial role in the development and metastasis of a wide range of carcinomas by regulating the expression of their target genes through various mechanisms causing translational repression or messenger RNA (mRNA) degradation. Along with miRNAs in the adrenocortical cancerous tissue, circulating miRNAs are considered barely invasive diagnostic or prognostic biomarkers of ACC. miRNAs may serve as treatment targets that expand the rather-limited therapeutic repertoire in the field of ACC. Patients with advanced ACC still have a poor prognosis when using the available treatments, despite a substantial improvement in understanding of the illness over the previous few decades. Accordingly, in this review, we provide a crucial overview of the recent studies in ACC-associated miRNAs regarding their diagnostic, prognostic, and potential therapeutic relevance.


Subject(s)
Adrenal Cortex Neoplasms , Adrenocortical Carcinoma , MicroRNAs , Humans , Adrenocortical Carcinoma/diagnosis , Adrenocortical Carcinoma/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Adrenal Cortex Neoplasms/diagnosis , Adrenal Cortex Neoplasms/genetics , Prognosis , Drug Resistance
13.
Life Sci ; 292: 120325, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-35031258

ABSTRACT

Exosomes are nano-vesicles (NVs) secreted by cells and take part in cell-cell communications. Lately, these exosomes were proved to have dual faces in cancer. Actually, they can contribute to carcinogenesis through epithelial-mesenchymal transition (EMT), angiogenesis, metastasis and tumor microenvironment (TME) of various cancers, including colorectal cancer (CRC). On the other hand, they can be potential targets for cancer treatment. CRC is one of the most frequent tumors worldwide, with incidence rates rising in the recent decades. In its early stage, CRC is asymptomatic with poor treatment outcomes. Therefore, finding a non-invasive, early diagnostic biomarker tool and/or suitable defender to combat CRC is mandatory. Exosomes provide enrichment and safe setting for their cargos non-coding RNAs (ncRNAs) and proteins, whose expression levels can be upregulated ordown-regulated in cancer. Hence, exosomes can be used as diagnostic and/or prognostic tools for cancer. Moreover, exosomes can provide a novel potential therapeutic modality for tumors via loading with specific chemotherapeutic agents, with the advantage of possible tumor targeting. In this review, we will try to collect and address recent studies concerned with exosomes and their cargos' implications for CRC diagnosis and/or hopefully, treatment.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinogenesis/metabolism , Colorectal Neoplasms/metabolism , Exosomes/metabolism , RNA, Long Noncoding/physiology , Gene Expression Regulation, Neoplastic , Humans
15.
Clin Biochem ; 70: 8-13, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31158358

ABSTRACT

BACKGROUND: Hepatitis C viral infection (HCV) and hepatocellular carcinoma (HCC) are potential health problems. New directly acting antivirals (DAAs) changed HCV treatment strategies. Selenoprotein P1 (SEPP1) is a hepatokine implicated in HCC pathogenesis. High mobility group box1 (HMGB1), a nuclear DNA-binding protein, involved in immune and inflammatory responses in HCV and HCC. Therefore, the aim of current study was to investigate HMGB1 and SEPP1 levels in HCV and HCV + HCC patients and exploring DAAs effect on them. METHODS: 15 healthy volunteers, 25 HCV and 25 HCV + HCC patients were included. Liver function tests, alpha fetoprotein (AFP), SEPP1 and HMGB1 serum levels were evaluated. For HCV group blood samples before and after treatment with sofosbuvir/daclatasvir combination were collected. RESULTS: HMGB1 was significantly higher in HCV + HCC group than in control and HCV groups (p < .05). SEPP1 decreased significantly in HCV and HCV + HCC groups compared to control group (p < .001). SEPP1 significantly elevated after treatment with DAAs (p = .001). HMGB1 and SEPP1 were negatively correlated with each other in HCV group (p = .047). Logistic regression analysis showed that HMGB1 and SEPP1 could be used as predictors for HCC in HCV infected patients (p = .02,p = .002) respectively. Receiver operating characteristic curve (ROC) revealed HMGB1 had 32% sensitivity and 100% specificity in differentiating HCV from HCV + HCC patients, both SEPP1 and HMGB1 had high sensitivity (92%,60%) and 93% specificity in differentiating healthy from HCV + HCC group. CONCLUSION: HMGB1 and SEPP1 are involved in pathogenesis of HCV and HCV induced HCC. Both of them could serve as predictive biomarkers for HCC in HCV patients.


Subject(s)
Antiviral Agents/therapeutic use , Biomarkers, Tumor/blood , Carcinoma, Hepatocellular/pathology , HMGB1 Protein/blood , Hepatitis C/drug therapy , Hepatitis C/metabolism , Liver Neoplasms/pathology , Selenoprotein P/blood , Adult , Case-Control Studies , Female , Humans , Male , Middle Aged
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