Natural products and long noncoding RNA signatures in gallbladder cancer: a review focuses on pathogenesis, diagnosis, and drug resistance.

Gallbladder cancer (GBC) is an aggressive and lethal malignancy with a poor prognosis. Long noncoding RNAs (lncRNAs) and natural products have emerged as key orchestrators of cancer pathogenesis through widespread dysregulation across GBC transcriptomes. Functional studies have revealed that lncRNAs interact with oncoproteins and tumor suppressors to control proliferation, invasion, metastasis, angiogenesis, stemness, and drug resistance. Curcumin, baicalein, oleanolic acid, shikonin, oxymatrine, arctigenin, liensinine, fangchinoline, and dioscin are a few examples of natural compounds that have demonstrated promising anticancer activities against GBC through the regulation of important signaling pathways. The lncRNAs, i.e., SNHG6, Linc00261, GALM, OIP5-AS1, FOXD2-AS1, MINCR, DGCR5, MEG3, GATA6-AS, TUG1, and DILC, are key players in regulating the aforementioned processes. For example, the lncRNAs FOXD2-AS1, DILC, and HOTAIR activate oncogenes such as DNMT1, Wnt/ß-catenin, BMI1, and c-Myc, whereas MEG3 and GATA6-AS suppress the tumor proteins NF-κB, EZH2, and miR-421. Clinically, specific lncRNAs can serve as diagnostic or prognostic biomarkers based on overexpression correlating with advanced TNM stage, metastasis, chemoresistance, and poor survival. Therapeutically, targeting aberrant lncRNAs with siRNA or antisense oligos disrupts their oncogenic signaling and inhibits GBC progression. Overall, dysfunctional lncRNA regulatory circuits offer multiple avenues for precision medicine approaches to improve early GBC detection and overcome this deadly cancer. They have the potential to serve as novel biomarkers as they are detectable in bodily fluids and tissues. These findings enhance gallbladder treatments, mitigating resistance to chemo- and radiotherapy.

Unveiling the regulatory role of miRNAs in stroke pathophysiology and diagnosis.

Stroke, a major global cause of mortality, leads to a range of problems for those who survive. Besides its brutal events, stroke also tends to have a characteristic of recurrence, making it a complex disease involving intricate regulatory networks. One of the major cellular regulators is the non-coding RNAs (ncRNA), specifically microRNAs (miRNAs), thus the possible functions of miRNAs in the pathogenesis of stroke are discussed as well as the possibility of using miRNA-based therapeutic approaches. Firstly, the molecular mechanisms by which miRNAs regulate vital physiological processes, including synaptic plasticity, oxidative stress, apoptosis, and the integrity of the blood-brain barrier (BBB) are reviewed. The miRNA indirectly impacts stroke outcomes by regulating BBB function and angiogenesis through the targeting of transcription factors and angiogenic factors. In addition, the tendency for some miRNAs to be upregulated in response to hypoxia, which is a prevalent phenomenon in stroke and various neurological disorders, highlights the possibility that it controls hypoxia-inducible factor (HIF) signaling and angiogenesis, thereby influencing the integrity of the BBB as examples of the discussed mechanisms. Furthermore, this review explores the potential therapeutic targets that miRNAs may offer for stroke recovery and highlights their promising capacity to alleviate post-stroke complications. This review provides researchers and clinicians with valuable resources since it attempts to decipher the complex network of miRNA-mediated mechanisms in stroke. Additionally, the review addresses the interplay between miRNAs and stroke risk factors as well as clinical applications of miRNAs as diagnostic and prognostic markers.

miRNAs as modulators of neuroinflammation and excitotoxicity: Implications for stroke therapeutics.

Stroke is a widespread neurological disorder associated with physical disabilities, mortality, and economic burden. In recent decades, substantial progress has been achieved in reducing the impact of this public health problem. However, further understanding of the pathophysiology of stroke and the underlying genetic pathways is required. The pathological mechanisms of stroke comprise multifaceted molecular cascades regulated by various microRNAs (miRNAs). An increasing number of studies have highlighted the role of miRNAs, which have received much attention during the last decades as an important class of post-transcriptional regulators. It was shown that miRNAs exert their role in the etiology of stroke via mediating excitotoxicity and neuroinflammation. Additionally, miRNAs could be helpful as non-invasive or minimally invasive biomarkers and therapeutic agents. Thus, the current review focused on the interplay of these miRNAs in stroke pathology to upgrade the existing therapeutic strategies.

Unraveling the role of miRNAs in the diagnosis, progression, and therapeutic intervention of Parkinson's disease.

Parkinson's disease (PD) is a debilitating neurological disorder characterized by the impairment of the motor system, resulting in symptoms such as resting tremor, cogwheel rigidity, bradykinesia, difficulty with gait, and postural instability. The occurrence of striatal dopamine insufficiency can be attributed to a notable decline in dopaminergic neurons inside the substantia nigra pars compacta. Additionally, the development of Lewy bodies serves as a pathological hallmark of PD. While current therapy approaches for PD aim to preserve dopaminergic neurons or replenish dopamine levels in the brain, it is important to acknowledge that achieving complete remission of the condition remains elusive. MicroRNAs (miRNAs, miR) are a class of small, non-coding ribonucleic acids involved in regulating gene expression at the post-transcriptional level. The miRNAs play a crucial part in the underlying pathogenic mechanisms of several neurodegenerative illnesses, including PD. The aim of this review is to explore the role of miRNAs in regulating genes associated with the onset and progression of PD, investigate the potential of miRNAs as a diagnostic tool, assess the effectiveness of targeting specific miRNAs as an alternative therapeutic strategy to impede disease advancement, and discuss the utilization of newly developed nanoparticles for delivering miRNAs as neurodegenerative therapies.

Deciphering signaling pathway interplay via miRNAs in malignant pleural mesothelioma.

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.

Association of XIST/miRNA155/Gab2/TAK1 cascade with the pathogenesis of anti-phospholipid syndrome and its effect on cell adhesion molecules and inflammatory mediators.

Anti-phospholipid syndrome (APS) is an autoimmune disease characterized by thrombosis and miscarriage events. Still, the molecular mechanisms underlying APS, which predisposes to a wide spectrum of complications, are being explored. Seventy patients with primary and secondary APS were recruited, in addition to 35 healthy subjects. Among APS groups, the gene expression levels of XIST, Gab2, and TAK1 were higher along with declined miRNA155 level compared with controls. Moreover, the sera levels of ICAM-1, VCAM-1, IL-1ꞵ, and TNF-α were highly elevated among APS groups either primary or secondary compared with controls. The lncRNA XIST was directly correlated with Gab2, TAK1, VCAM-1, ICAM-1, IL-1ꞵ, and TNF-α. The miRNA155 was inversely correlated with XIST, Gab2, and TAK1. Moreover, ROC curve analyses subscribed the predictive power of the lncRNA XIST and miRNA155, to differentiate between primary and secondary APS from control subjects. The lncRNA XIST and miRNA155 are the upstream regulators of the Gab2/TAK1 axis among APS patients via influencing the levels of VCAM-1, ICAM-1, IL1ꞵ, and TNF-α which propagates further inflammatory and immunological streams. Interestingly, the study addressed that XIST and miRNA155 may be responsible for the thrombotic and miscarriage events associated with APS and provides new noninvasive molecular biomarkers for diagnosing the disease and tracking its progression.

Melodic maestros: Unraveling the role of miRNAs in the diagnosis, progression, and drug resistance of malignant pleural mesothelioma.

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.

The emerging role of miRNAs in Merkel cell carcinoma pathogenesis: Signaling pathway crosstalk.

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.

miRNAs driving diagnosis, prognosis and progression in Merkel cell carcinoma.

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.

Suppression of NLRP3 inflammasome by ivermectin ameliorates bleomycin-induced pulmonary fibrosis. / ä¼Šç»´èŒç´ æŠ‘åˆ¶NLRP3ç‚Žç—‡å°ä½“å¯æ”¹å–„åšæ¥éœ‰ç´ è¯±å¯¼çš„è‚ºçº¤ç»´åŒ–.

Ivermectin is a US Food and Drug Administration (FDA)-approved antiparasitic agent with antiviral and anti-inflammatory properties. Although recent studies reported the possible anti-inflammatory activity of ivermectin in respiratory injuries, its potential therapeutic effect on pulmonary fibrosis (PF) has not been investigated. This study aimed to explore the ability of ivermectin (0.6 mg/kg) to alleviate bleomycin-induced biochemical derangements and histological changes in an experimental PF rat model. This can provide the means to validate the clinical utility of ivermectin as a treatment option for idiopathic PF. The results showed that ivermectin mitigated the bleomycin-evoked pulmonary injury, as manifested by the reduced infiltration of inflammatory cells, as well as decreased the inflammation and fibrosis scores. Intriguingly, ivermectin decreased collagen fiber deposition and suppressed transforming growth factor-|ß1 (TGF-|ß1) and fibronectin protein expression, highlighting its anti-fibrotic activity. This study revealed for the first time that ivermectin can suppress the nucleotide-binding oligomerization domain (NOD)|-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, as manifested by the reduced gene expression of NLRP3 and the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), with a subsequent decline in the interleukin|-|1ß (IL|-|1ß) level. In addition, ivermectin inhibited the expression of intracellular nuclear factor-|κB (NF|-|κB) and hypoxia­inducible factor­1α (HIF|-|1α) proteins along with lowering the oxidative stress and apoptotic markers. Altogether, this study revealed that ivermectin could ameliorate pulmonary inflammation and fibrosis induced by bleomycin. These beneficial effects were mediated, at least partly, via the downregulation of TGF-|ß1 and fibronectin, as well as the suppression of NLRP3 inflammasome through modulating the expression of HIF­1α and NF-|κB.

The potential role of miRNAs in the pathogenesis of adrenocortical carcinoma - A focus on signaling pathways interplay.

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.

Acovenoside A as a novel therapeutic approach to boost taxol and carboplatin apoptotic and antiproliferative activities in NSCLC: Interplay of miR-630/miR-181a and apoptosis genes.

The aim of the present study is to explore the potential anticancer effect of the cardenolide; acovenoside A against non-small cell lung cancer (NSCLC), understand its molecular mechanism in inducing apoptosis and show the effect of its combination with carboplatin and taxol. MTT assay showed that the combination of acovenoside A with taxol and carboplatin caused 78.9% cytotoxicity reflecting the synergistic effect. The triple combination showed the best growth inhibition efficiency where the number of cells at the G2/M phase was decreased and boosted up apoptotic and necrotic activity. The combination also showed the most remarkable increase in gene expression of Bax and p53 and the least level of Bcl2. The gene expression of miRNA181a and miRNA630 was significantly upregulated in cell lines treated with the combination. The present study has proven that the underlying mechanism of acovenoside A is partially attributed to the upregulation of miR-630 and miR-181a gene expressions which in turn targets the intrinsic apoptosis genes as p53, Bax and Bcl2 as well as caspase 3. The present study is the first to address the valuable effect of using acovenoside A together with carboplatin and taxol in the treatment of NSCLC via exerting apoptotic, antiproliferative, and cytotoxic effects..

miRNAs orchestration of adrenocortical carcinoma - Particular emphasis on diagnosis, progression and drug resistance.

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.

The lncRNAs UCA1 and CRNDE target miR-145/TLR4/NF-қB/TNF-α axis in acetic acid-induced ulcerative colitis model: The beneficial role of 3,3-Diindolylmethane.

INTRODUCTION: Ulcerative colitis (UC) is a chronic disease that alters the colonic and rectal mucosa. The high prevalence rates of UC make it a worldwide healthcare problem. However, its underlying molecular mechanisms remain vague. AIM OF THE STUDY: To investigate the molecular mechanisms underlying UC and to study the cross-talk among the regulatory role of the lncRNAs UCA1, CRNDE, and miR-145 on TLR4/NF-κB/TNF-α signaling pathway. Moreover, the study was extended to examine the beneficial effects of 3,3-Diindolylmethane (DIM) on relieving UC. METHODS: UC was induced in rats by injecting 2 ml of 4% acetic acid (AA) solution transrectally. After 24 h, rats were treated with either DIM (20 mg/kg) or sulphasalazine (SSZ) (500 mg/kg) orally for 7 days. RESULTS: The present study revealed that the gene expression of the lncRNAs UCA1 and CRNDE were significantly upregulated in the AA-induced UC model compared with the control group, whereas miR-145 was significantly downregulated. There was a significant association between the expression of these non-coding RNAs and TLR4/ NF-κB/TNF-α axis as well as malondialdehyde and glutathione levels. Favorably, the DIM-treated group showed significant downregulation of the lncRNAs UCA1 and CRNDE along with upregulated miR-145 compared with the AA-induced UC model. Furthermore, DIM showed remarkable inhibition of the TLR4/ NF-κB /TNF-α cascade compared with non-treated UC rats. CONCLUSIONS: The present study is the first to document the interrelated role of the lncRNAs UCA1 and CRNDE in UC via orchestrating miR-145/TLR4/ NF-κB /TNF-α inflammatory cascade. Furthermore, the study demonstrated a new molecular basis for the pleiotropic activities of DIM in relieving UC.

The potential role of miRNAs in the pathogenesis of salivary gland cancer - A Focus on signaling pathways interplay.

Salivary gland cancer (SGC) is immensely heterogeneous, both in terms of its physical manifestation and its aggressiveness. Developing a novel diagnostic and prognostic detection method based on the noninvasive profiling of microribonucleic acids (miRs) could be a goal for the clinical management of these specific malignancies, sparing the patients' valuable time. miRs are promising candidates as prognostic biomarkers and therapeutic targets or factors that can advance the therapy of SGC due to their ability to posttranscriptionally regulate the expression of various genes involved in cell proliferation, differentiation, cell cycle, apoptosis, invasion, and angiogenesis. Depending on their biological function, many miRs may contribute to the development of SGC. Therefore, this article serves as an accelerated study guide for SGC and the biogenesis of miRs. Here, we shall list the miRs whose function in SGC pathogenesis has recently been determined with an emphasis on their potential applications as therapeutic targets. We will also offer a synopsis of the current state of knowledge about oncogenic and tumor suppressor miRs in relation to SGC.

miRNAs orchestration of salivary gland cancer- Particular emphasis on diagnosis, progression, and drug resistance.

Cancer of the salivary glands is one of the five major types of head and neck cancer. Due to radioresistance and a strong propensity for metastasis, the survival rate for nonresectable malignant tumors is dismal. Hence, more research is needed on salivary cancer's pathophysiology, particularly at the molecular level. The microRNAs (miRNAs) are a type of noncoding RNA that controls as many as 30% of all genes that code for proteins at the posttranscriptional level. Signature miRNA expression profiles have been established in several cancer types, suggesting a role for miRNAs in the incidence and progression of human malignancies. Salivary cancer tissues were shown to have significantly aberrant levels of miRNAs compared to normal salivary gland tissues, supporting the hypothesis that miRNAs play a crucial role in the carcinogenesis of salivary gland cancer (SGC). Besides, several SGC research articles reported potential biomarkers and therapeutic targets for the miRNA-based treatment of this malignancy. In this review, we will explore the regulatory impact of miRNAs on the processes underlying the molecular pathology of SGC and provide an up-to-date summary of the literature on miRNAs that impacted this malignancy. We will eventually share information about their possible use as diagnostic, prognostic, and therapeutic biomarkers in SGC.

Implication of Wnt/GSK-3ß/ß-Catenin Signaling in the Pathogenesis of Mood Disturbances Associated with Hyperthyroidism in Rats: Potential Therapeutic Effect of Naringin.

Patients with hyperthyroidism are commonly diagnosed with mood disorders. Naringin, (4',5,7-trihydrocyflavanone-7-O-rhamnoglucoside), a natural bioflavonoid, has many neurobehavioral activities including anxiolytic and antidepressant properties. The role of Wingless (Wnt) signaling in psychiatric disorders is considered substantial but debatable. Recently, regulation of Wnt signaling by naringin has been reported in different disorders. Therefore, the present study aimed to investigate the possible role of Wnt/GSK-3ß/ß-catenin signaling in hyperthyroidism-induced mood disturbances and explore the therapeutic effects of naringin. Hyperthyroidism was induced in rats by intraperitoneal injection of 0.3 mg/kg levothyroxine for 2 weeks. Naringin was orally administered to rats with hyperthyroidism at a dose of 50 or 100 mg/kg for 2 weeks. Hyperthyroidism induced mood alterations as revealed by behavioral tests and histopathological changes including marked necrosis and vacuolation of neurons in the hippocampus and cerebellum. Intriguingly, hyperthyroidism activated Wnt/p-GSK-3ß/ß-catenin/DICER1/miR-124 signaling pathway in the hippocampus along with an elevation in serotonin, dopamine, and noradrenaline contents and a reduction in brain-derived neurotrophic factor (BDNF) content. Additionally, hyperthyroidism induced upregulation of cyclin D-1 expression, malondialdehyde (MDA) elevation, and glutathione (GSH) reduction. Naringin treatment alleviated behavioral and histopathological alterations and reversed hyperthyroidism-induced biochemical changes. In conclusion, this study revealed, for the first time, that hyperthyroidism could affect mental status by stimulating Wnt/p-GSK-3ß/ß-catenin signaling in the hippocampus. The observed beneficial effects of naringin could be attributed to increasing hippocampal BDNF, controlling the expression of Wnt/p-GSK-3ß/ß-catenin signaling as well as its antioxidant properties.

miRNAs role in glioblastoma pathogenesis and targeted therapy: Signaling pathways interplay.

High mortality and morbidity rates and variable clinical behavior are hallmarks of glioblastoma (GBM), the most common and aggressive primary malignant brain tumor. Patients with GBM often have a dismal outlook, even after undergoing surgery, postoperative radiation, and chemotherapy, which has fueled the search for specific targets to provide new insights into the development of contemporary therapies. The ability of microRNAs (miRNAs/miRs) to posttranscriptionally regulate the expression of various genes and silence many target genes involved in cell proliferation, cell cycle, apoptosis, invasion, angiogenesis, stem cell behavior and chemo- and radiotherapy resistance makes them promising candidates as prognostic biomarkers and therapeutic targets or factors to advance GBM therapeutics. Hence, this review is like a crash course in GBM and how miRNAs related to GBM. Here, we will outline the miRNAs whose role in the development of GBM has been established by recent in vitro or in vivo research. Moreover, we will provide a summary of the state of knowledge regarding oncomiRs and tumor suppressor (TS) miRNAs in relation to GBM with an emphasis on their potential applications as prognostic biomarkers and therapeutic targets.

Telomerase RNA component lncRNA as potential diagnostic biomarker promotes CRC cellular migration and apoptosis evasion via modulation of ß-catenin protein level.

Aim: Long non-coding RNA (LncRNA) telomerase RNA component (TERC) has telomerase-dependent and independent activity in numerous cancer types. The present study purposes to demonstrate the role of lncRNA TERC as a diagnostic serum biomarker in colorectal cancer (CRC) patients and the molecular mechanism of lncRNA TERC in inducing tumor in CRC cell lines. Materials and methods: PCR array was performed to examine lncRNAs dysregulated in CRC. LncRNA TERC expression level was evaluated in 70 CRC patients and 35 control subjects using RT-qPCR. Then transfection was performed to build down-expression models of lncRNA TERC. ROC curve analysis was applied to assess the diagnostic value of serum LncRNA CRC. In addition, RT-qPCR was used to detect expression level of lncRNA TERC and ß-catenin mRNA. Moreover, ELISA and Western blot were used to detect the level of ß-catenin protein in sera of CRC patients and cell lines. The biological functions such as cell growth and migration of CRC cells were assessed using a wound healing assay. Cell cycle analysis and apoptosis analysis were performed using flow cytometry. Results: The lncRNA TERC is overexpressed in the sera of CRC patients with high diagnostic and stage discrimination accuracy. Furthermore, lncRNA TERC expression was upregulated in CRC cell lines and lncRNA TERC silencing induced cell arrest and apoptosis and inhibited cell migration. Furthermore, inhibition of lncRNA TERC reduces ß-catenin protein levels. Conclusion: The lncRNA TERC could be considered as an early stages CRC diagnostic biomarker with a good ability to discriminate between CRC stages. lncRNA TERC induces CRC by promoting cell migration and evading apoptosis by elevating the level of ß-catenin protein.

MAGI2-AS3 and miR-374b-5p as Putative Regulators of Multiple Sclerosis via Modulating the PTEN/AKT/IRF-3/IFN-ß Axis: New Clinical Insights.

Multiple sclerosis (MS) is a chronic disease and one of the leading causes of disability in young adults. The current study aims to investigate the pathogenesis of MS via studying the regulatory role of novel lncRNA MAGI2-AS3 in miR-374b-5p and their downstream targets PTEN/AKT/IRF-3/IFN-ß and the relationship of this pathway with disease severity. Moreover, it aims to assess the role of MAGI2-AS3/miR-374b-5p as diagnostic and/or prognostic biomarkers for MS. Overall, 150 contributors were recruited: 100 patients with MS and 50 healthy volunteers. Gene expression of MAGI2-AS3, miR-374b-5p, PTEN, AKT, and IRF-3 were assessed using RT-qPCR, and IFN-ß was measured by ELISA. Compared with the healthy control group, serum MAGI2-AS3 and PTEN were downregulated in MS patients, whereas miR-374b-5p, PI3K, AKT, IRF-3, and IFN-ß were upregulated in MS patients. Furthermore, MAGI2-AS3 was downregulated, while miR-374b-5p was upregulated in MS patients with an expanded disability status scale (EDSS) ≥3.5, compared to patients with an EDSS <3.5. Receiver-operating-characteristic curve analysis revealed that MAGI2-AS3 and miR-374b-5p can be used in the diagnosis of MS. Remarkably, multivariate logistic analysis revealed that MAGI2-AS3, miR-374b-5p, PTEN, and AKT act as independent variables in MS. Moreover, MAGI2-AS3 was directly correlated with PTEN and inversely correlated with miR-374b-5p, AKT, and EDSS. Regarding miR-374b-5p, it was positively correlated with AKT and EDSS. In conclusion, the study showed for the first time that the crosstalk between MAGI2-AS3 and miR-374b-5p could affect the AKT/IRF3/IFN-ß axis in MS. Interestingly, MAGI2-AS3 and miR-374b-5p could be genetic noninvasive biomarkers for MS.