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Review of early circulating biomolecules associated with diabetes nephropathy - Ideal candidates for early biomarker array test for DN

Quan KY, Yap CG, Jahan NK, Pillai N

Diabetes Res Clin Pract, 2021 Dec;182:109122.
PMID: 34742785 DOI: 10.1016/j.diabres.2021.109122

BACKGROUND: Diabetic nephropathy (DN) is one of the catastrophic complications of type 2 diabetes mellitus (T2DM). 45% of DN patients progressed to End Stage Renal Disease (ESRD) which robs casualties of the quality of live. The challenge in early diagnosis of DN is it is asymptomatic in the early phase. Current gold standard test for screening and diagnosis of DN are nonspecific and are not sensitive in detecting DN early enough and subsequently monitor renal function during management and intervention plans. Recent studies reported various biomolecules which are associated with the onset of DN in T2DM using cutting-edge technologies. These biomolecules could be potential early biomarkers for DN. This review selectively identified potential early serum biomolecules which are potential candidates for developing an Early Biomarker Array Test for DN.
METHODS: An advanced literature search was conducted on 4 online databases. Search terms used were "Diabetes Mellitus, Type 2", "Diabetic nephropathy", "pathogenesis" and "early biomarker. Filters were applied to capture articles published from 2010 to 2020, written in English, human or animal models and focused on serum biomolecules associated with DN.
RESULTS: Five serum biomolecules have been evidently described as contributing pivotal roles in the pathophysiology of DN. MiR-377, miR-99b, CYP2E1, TGF-β1 and periostin are potential candidates for designing an early biomarker array for screening and diagnosis of early stages of DN. The five shortlisted biomolecules originates from endogenous biochemical processes which are specific to the progressive pathophysiology of DN.
CONCLUSION: miR-377, miR-99b, CYP2E1, TGF-β1 and periostin are potential candidate biomolecules for diagnosing DN at the early phases and can be developed into a panel of endogenous biomarkers for early detection of DN in patients with T2DM. The outcomes of this study will be a stepping stone towards planning and developing an early biomarker array test for diabetic nephropathy. The proposed panel of early biomarkers for DN has potential of stratifying the stages of DN because each biomolecule appears at distinct stages in the pathophysiology of DN.

Matched MeSH terms: MicroRNAs*
Methylated MicroRNA Biomarkers for Identifying Ulcerative Colitis-Associated Colorectal Cancers

Mahakkanukrauh P, Sinthubua A, Das S

Gastroenterology, 2018 05;154(6):1852.
PMID: 29621516 DOI: 10.1053/j.gastro.2017.12.048
Matched MeSH terms: MicroRNAs*
Fulltext MicroRNA expression in antiphospholipid syndrome: a systematic review and microRNA target genes analysis

Muhammad Shazwan S, Muhammad Aliff M, Asral Wirda AA, Hayati AR, Maizatul Azma M, Nur Syahrina AR, et al.

Malays J Pathol, 2016 Dec;38(3):273-283.
PMID: 28028298 MyJurnal

INTRODUCTION: Antiphospholipid antibodies (aPL) are autoantibodies that attack phospholipid through anti-beta 2-glycoprotein 1. The actions of aPL are associated with events leading to thrombosis and morbidity in pregnancy. Antiphospholipid syndrome (APS) is diagnosed when a patient is persistently positive for aPL and also has recognised clinical manifestations such as recurrent pregnancy losses, arterial or venous thrombosis and in a catastrophic case, can result in death. Unfortunately, the pathogenesis of APS is still not well established. Recently, microRNA expressed in many types of diseased tissues were claimed to be involved in the pathological progression of diseases and has become a useful biomarker to indicate diseases, including APS.

OBJECTIVE: This systematic review aims to search for research papers that are focussing on microRNA expression profiles in APS.

METHOD: Three search engines (Ebcohost, ProQuest and Ovid) were used to identify papers related to expression of specific microRNA in antiphospholipid syndrome.

RESULTS AND DISCUSSION: A total of 357 papers were found and screened, out of which only one study fulfilled the requirement. In this particular study blood samples from APS patients were tested. The microRNAs found to be related to APS were miR-19b and miR-20a. No data was found on specific microRNA being expressed in obstetric antiphospholipid syndrome. Analysis on the microRNA target genes revealed that most genes targeted by miR-19b and miR-20a involve in TGF-Beta Signalling and VEGF, hypoxia and angiogenesis pathways.

CONCLUSION: In view of the limited data on the expressions of microRNA in APS we recommend further research into this field. Characterization of microRNA profile in blood as well as in placenta tissue of patients with APS could be useful in identifying microRNAs involved in obstetric APS.

Matched MeSH terms: MicroRNAs/biosynthesis*
Fulltext Circulating miRNAs in Type 2 Diabetic Patients with and without Albuminuria in Malaysia

Zahari Sham SY, Ng CT, Azwar S, Yip WK, Abdullah M, Thevandran K, et al.

Kidney Blood Press Res, 2022;47(2):81-93.
PMID: 35158353 DOI: 10.1159/000518866

INTRODUCTION: Diabetic kidney disease (DKD) remains the leading cause of chronic kidney disease. Dysregulation of circulating miRNAs has been reported, suggesting their pathological roles in DKD. This study aimed to investigate differentially expressed miRNAs in the sera of type 2 diabetes mellitus (T2DM) patients with and without albuminuria in a selected Malaysian population.
METHOD: Forty-one T2DM patients on follow-up at a community clinic were divided into normo-(NA), micro-(MIC), and macroalbuminuria (MAC) groups. Differential levels of miRNAs in 12 samples were determined using the pathway-focused (human fibrosis) miScript miRNA qPCR array and was validated in 33 samples, using the miScript custom qPCR array (CMIHS02742) (Qiagen GmbH, Hilden, Germany).
RESULTS: Trends of upregulation of 3 miRNAs in the serum, namely, miR-874-3p, miR-101-3p, and miR-145-5p of T2DM patients with MAC compared to those with NA. Statistically significant upregulation of miR-874-3p (p = 0.04) and miR-101-3p (p = 0.01) was seen in validation cohort. Significant negative correlations between the estimated glomerular filtration rate (eGFR) and miR-874-3p (p = 0.05), miR-101-3p (p = 0.03), and miR-145-5p (p = 0.05) as well as positive correlation between miR-874-3p and age (p = 0.03) were shown by Pearson's correlation coefficient analysis.
CONCLUSION: Upregulation of previously known miRNA, namely, miR-145-5p, and possibly novel ones, namely, miR-874-3p and miR-101-3p in the serum of T2DM patients, was found in this study. There was a significant correlation between the eGFR and these miRNAs. The findings of this study have provided encouraging evidence to further investigate the putative roles of these differentially expressed miRNAs in DKD.

Matched MeSH terms: MicroRNAs*
Plasma miR-146a and miR-365 expression and inflammatory factors in patients with osteoarthritis

Wu W, Xuan Y, Ge Y, Mu S, Hu C, Fan R

Malays J Pathol, 2021 Aug;43(2):311-317.
PMID: 34448795

OBJECTIVE: To investigate the expression levels of micro-ribonucleic acid (miR)-146a and miR-365 in the plasma of osteoarthritis (OA) patients, to study their expression with the inflammatory factors and the severity of disease in patients and to analyse their diagnostic significance.
MATERIALS AND METHODS: A total of 42 OA patients diagnosed with OA and treated in our hospital from January 2017 to January 2018 were selected as the subjects, and 28 healthy people were enrolled as controls. The expressions of interleukin-1 beta (IL-1β) and IL-6 in the plasma of OA patients were detected via immunohistochemical staining. Moreover, the knee joint function of OA patients was evaluated by Lysholm score, Western Ontario and McMaster Universities (WOMAC) score and Visual Analogue Scale (VAS) score. The expression levels of plasma miR-146a and miR-365 in OA patients were measured through RT-PCR. Besides, the significance of the expression levels of miR-146a and miR-365 for the diagnosis of OA was analysed by ROC curves.
RESULTS: As compared with healthy people, OA patients had elevated expression levels of plasma IL-1β and IL-6, decreased Lysholm score, increased WOMAC and VAS scores as well as significantly up-regulated levels of plasma miR-146a and miR-365, which were of important significance for diagnosis.
CONCLUSION: The expression levels of plasma miR-146a, miR-365 and inflammatory factors are notably higher, the disease is more severe, and the function of knee joint movement is weaker in OA patients than those in healthy controls. It can be concluded that the levels of both miR-146a and miR-365 can serve as biomarkers of OA diagnosis.

Matched MeSH terms: MicroRNAs/genetics*
Expression Profile of Circulating Exosomal microRNAs in Leukoplakia, Oral Submucous Fibrosis, and Combined Lesions of Leukoplakia and Oral Submucous Fibrosis

Yasothkumar D, Ramani P, Jayaraman S, Ramalingam K, Tilakaratne WM

Head Neck Pathol, 2024 Mar 27;18(1):28.
PMID: 38536520 DOI: 10.1007/s12105-024-01627-4

OBJECTIVES: This study aims to elucidate the expression of circulating exosomal miRNAs miRNA 21, miRNA 184, and miRNA 145 in the studied groups, including patients with (i) leukoplakia; (ii) oral submucous fibrosis; (iii) oral submucous fibrosis with leukoplakia; (iv) oral squamous cell carcinoma; and (v) healthy individuals.
STUDY DESIGN: An observational study was conducted among 54 patients who reported to the outpatient department of Saveetha Dental College and Hospitals. The patients were divided into three groups: Group I healthy individuals (n = 18), Group II: case group (leukoplakia, OSMF, and leukoplakia and OSMF) (n = 18), and Group III: OSCC (n = 18). Real-time polymerase chain reaction analysis was carried out to assess the expression profiles of miRNA 21, miRNA 184, and miRNA 145. The statistical analysis was calculated using SPSS software version 23.
RESULTS: All three miRNAs showed a statistically significant difference in the one-way ANOVA test between the case group (leukoplakia, OSMF, and leukoplakia and OSMF), healthy group, and OSCC group (p

Matched MeSH terms: MicroRNAs*
Metal-organic framework (MOF)-based biosensors for miRNA detection

Gorgani L, Mohammadi M, Najafpour Darzi G, Raoof JB

Talanta, 2024 Jun 01;273:125854.
PMID: 38447342 DOI: 10.1016/j.talanta.2024.125854

MicroRNAs (miRNAs) play several crucial roles in the physiological and pathological processes of the human body. They are considered as important biomarkers for the diagnosis of various disorders. Thus, rapid, sensitive, selective, and affordable detection of miRNAs is of great importance. However, the small size, low abundance, and highly similar sequences of miRNAs impose major challenges to their accurate detection in biological samples. In recent years, metal-organic frameworks (MOFs) have been applied as promising sensing materials for the fabrication of different biosensors due to their distinctive characteristics, such as high porosity and surface area, tunable pores, outstanding adsorption affinities, and ease of functionalization. In this review, the applications of MOFs and MOF-derived materials in the fabrication of fluorescence, electrochemical, chemiluminescence, electrochemiluminescent, and photoelectrochemical biosensors for the detection of miRNAs and their detection principle and analytical performance are discussed. This paper attempts to provide readers with a comprehensive knowledge of the fabrication and sensing mechanisms of miRNA detection platforms.

Matched MeSH terms: MicroRNAs*
MicroRNAs horizon in retinoblastoma

Mirakholi M, Mahmoudi T, Heidari M

Acta Med Iran, 2013;51(12):823-9.
PMID: 24442535

In the retinoblastoma research, it is of great interest to identify molecular markers associated with the genetics of tumorigenesis. microRNAs (miRNAs) are small non-coding RNA molecules that play a regulatory role in many crucial cellular pathways such as differentiation, cell cycle progression, and apoptosis. A body of evidences showed dysregulation of miRNAs in tumor biology and many diseases. They potentially play a significant role in tumorigenesis processes and have been the subject of research in many types of cancers including retinal tumorigenesis. miRNA expression profiling was found to be associated with tumor development, progression and treatment. These associations demonstrate the putative applications of miRNAs in monitoring of different aspect of tumors consisting diagnostic, prognostic and therapeutic. Herein, we review the current literature concerning to the study of miRNA target recognition, function to tumorigenesis and treatment in retinoblastoma. Identification the specific miRNA biomarkers associated with retinoblastoma cancer may help to establish new therapeutic approaches for salvage affected eyes in patients.

Matched MeSH terms: MicroRNAs/genetics; MicroRNAs/physiology*
PLASMA MICRORNA-133А LEVEL IN PATIENTS WITH ESSENTIAL ARTERIAL HYPERTENSION

Koval S, Snihurska I, Yushko K, Lytvynova O, Berezin A

Georgian Med News, 2019 May.
PMID: 31322515

The aim of research was to investigate the plasma microRNA (miR-133а) level in patients with essential arterial hypertension (EAH). A total of 45 patients with EAH 2-3 degrees aged 52.14 ± 8.25 years and 21 healthy individuals (control group) with comparable age and sex distributions. The following frequency of risk factors was revealed among the examined patients: overweight (53%), dyslipidaemia (73%), pre-diabetes (13%), asymptomatic hyperuricemia (29%); hypertension-mediated organ damage: increased arterial stiffness (27%), left ventricular hypertrophy (55%), atherosclerotic plaque in the carotid artery (40%), microalbuminuria (15%), moderate stage of chronic kidney disease (22%) and cardiovascular diseases: stable ischemic heart disease (11%) and heart failure with preserved ejection fraction of NYHA functional class I (18%). The plasma miR-133a level was determined by polymerase chain reaction using "CFX96 Touch" detection system (BioRad) and "TaqMan microRNA Assay" and "TaqMan® Universal PCR Master Mix" reagents (Thermo Fisher Scientific, USA). It has been established that in patients with EAH the plasma level of miR-133a was significantly lower than in practically healthy individuals (0,182 [0,102; 0,301] ), vs (0,382 [0,198; 0,474]), p <0.05). It has also been revealed a significant decrease in the level of miR-133a in the blood plasma in patients with such organs damage as LVH (0,133 [0,099;0,184]) in comparison with patients without LVH (0,238 [0,155; 0,410]), p <0.05) and also significantly lower than in healthy subjects in the control group (0,382 [0,198; 0,474]), p<0.05). There were no statistically significant differences in the plasma levels of miR-133a in the group of patients with EAH, depending on the presence of risk factors, other organ damage and cardiovascular diseases. The findings suggest the significant role of reducing of plasma levels of miR-133a in the pathogenesis of hypertension itself and in pathological remodeling of the heart.

Matched MeSH terms: MicroRNAs/blood*; MicroRNAs/genetics
Association of Micro RNA and Postoperative Cognitive Dysfunction: A Review

Yazit NAA, Juliana N, Das S, Teng NIMF, Fahmy NM, Azmani S, et al.

Mini Rev Med Chem, 2020;20(17):1781-1790.
PMID: 32564754 DOI: 10.2174/1389557520666200621182717

Postoperative Cognitive Dysfunction (POCD) refers to the condition of neurocognitive decline following surgery in a cognitive and sensory manner. There are several risk factors, which may be life-threatening for this condition. Neuropsychological assessment of this condition is very important. In the present review, we discuss the association of apolipoprotein epsilon 4 (APOE ε4) and few miRNAs with POCD, and highlight the clinical importance for prognosis, diagnosis and treatment of POCD. Microarray is a genome analysis that can be used to determine DNA abnormalities. This current technique is rapid, efficient and high-throughout. Microarray techniques are widely used to diagnose diseases, particularly in genetic disorder, chromosomal abnormalities, mutations, infectious diseases and disease-relevant biomarkers. MicroRNAs (miRNAs) are a class of non-coding RNAs that are widely found distributed in eukaryotes. Few miRNAs influence the nervous system development, and nerve damage repair. Microarray approach can be utilized to understand the miRNAs involved and their pathways in POCD development, unleashing their potential to be considered as a diagnostic marker for POCD. This paper summarizes and identifies the studies that use microarray based approaches for POCD analysis. Since the application of microarray in POCD is expanding, there is a need to review the current knowledge of this approach.

Matched MeSH terms: MicroRNAs/genetics; MicroRNAs/metabolism*
Fulltext IsomiRs have functional importance

Tan GC, Dibb N

Malays J Pathol, 2015 Aug;37(2):73-81.
PMID: 26277662 MyJurnal

Since the inception of deep sequencing, isomiRs are consistently observed to be produced by most miRNA genes in a variety of cell types. IsomiRs appear as a variation in length from the canonical sequence annotated in miRBase, due to an addition or deletion of one or more nucleotides at the 5(') or 3(') ends or both. As the seed sequence is located at the 5(') end of the microRNA, the target mRNA will be theoretically different. Therefore, 5(')isomiRs might potentially target a new set mRNA compared to their canonical counterpart. This article gives an overview of investigations that explored the functional potential of isomiRs such as their ability to incorporate into Argonaute protein, the differential expression of isomiRs in various tissue types and cell lines, and the differences of mRNA targets between isomiR and its canonical microRNA. In addition, this article provides a brief introduction of RNA sponges as a potential way to inhibit isomiRs.

Matched MeSH terms: MicroRNAs/genetics*
Fulltext Evaluation of extraction kits and RT-qPCR systems adapted to high-throughput platform for circulating miRNAs

Tan GW, Khoo AS, Tan LP

Sci Rep, 2015;5:9430.
PMID: 25800946 DOI: 10.1038/srep09430

MicroRNAs regulate gene expression at the post-transcriptional level. Differential expression of miRNAs can potentially be used as biomarkers for early diagnosis and prediction for outcomes. Failure in validation of miRNA profiles is often caused by variations in experimental parameters. In this study, the performance of five extraction kits and three RT-qPCR systems were evaluated using BioMark high-throughput platform and the effects of different experimental parameters on circulating miRNA levels were determined. Differences in the performance of extraction kits as well as varying accuracy, sensitivity and reproducibility in qPCR systems were observed. Normalisation of RT-qPCR data to spike-in controls can reduce extraction bias. However, the extent of correlation for different qPCR systems varies in different assays. At different time points, there was no significant fold change in eight of the plasma miRNAs that we evaluated. Higher level of miRNAs was detected in plasma as compared to serum of the same cohort. In summary, we demonstrated that high-throughput RT-qPCR with pre-amplification step had increased sensitivity and can be achieved with accuracy and high reproducibility through stringent experimental controls. The information provided here is useful for planning biomarker validation studies involving circulating miRNAs.

Matched MeSH terms: MicroRNAs/genetics*
Role of miRNAs in regulating responses to radiotherapy in human breast cancer

Chong ZX, Yeap SK, Ho WY

Int J Radiat Biol, 2021;97(3):289-301.
PMID: 33356761 DOI: 10.1080/09553002.2021.1864048

Breast cancer is the most common type of cancer that affects females globally. Radiotherapy is a standard treatment option for breast cancer, where one of its most significant limitations is radioresistance development. MicroRNAs (miRNAs) are small, non-protein-coding RNAs that have been widely studied for their roles as disease biomarkers. To date, several in vitro, in vivo, and clinical studies have reported the roles of miRNAs in regulating radiosensitivity and radioresistance in breast cancer cells. This article reviews the roles of miRNAs in regulating treatment response toward radiotherapy and the associating cellular pathways. We identified 36 miRNAs that play a role in mediating radio-responses; 22 were radiosensitizing, 12 were radioresistance-promoting, and two miRNAs were reported to promote both effects. A brief overview of breast cancer therapy options, mechanism of action of radiation, and molecular mechanism of radioresistance was provided in this article. A summary of the latest clinical researches involving miRNAs in breast cancer radiotherapy was also included.

Matched MeSH terms: MicroRNAs/physiology*
Causes and Consequences of MicroRNA Dysregulation Following Cerebral Ischemia-Reperfusion Injury

Forouzanfar F, Shojapour M, Asgharzade S, Amini E

CNS Neurol Disord Drug Targets, 2019;18(3):212-221.
PMID: 30714533 DOI: 10.2174/1871527318666190204104629

Stroke continues to be a major cause of death and disability worldwide. In this respect, the most important mechanisms underlying stroke pathophysiology are inflammatory pathways, oxidative stress, as well as apoptosis. Accordingly, miRNAs are considered as non-coding endogenous RNA molecules interacting with their target mRNAs to inhibit mRNA translation or reduce its transcription. Studies in this domain have similarly shown that miRNAs are strongly associated with coronary artery disease and correspondingly contributed to the brain ischemia molecular processes. To retrieve articles related to the study subject, i.e. the role of miRNAs involved in inflammatory pathways, oxidative stress, and apoptosis in stroke from the databases of Web of Science, PubMed (NLM), Open Access Journals, LISTA (EBSCO), and Google Scholar; keywords including cerebral ischemia, microRNA (miRNA), inflammatory pathway, oxidative stress, along with apoptosis were used. It was consequently inferred that, miRNAs could be employed as potential biomarkers for diagnosis and prognosis, as well as therapeutic goals of cerebral ischemia.

Matched MeSH terms: MicroRNAs/metabolism*
Fulltext Efficacy of zinc carnosine in the treatment of colorectal cancer and its potential in combination with immunotherapy in vivo

Tang W, Liu H, Li X, Ooi TC, Rajab NF, Cao H, et al.

Aging (Albany NY), 2022 Nov 14;14(21):8688-8699.
PMID: 36375474 DOI: 10.18632/aging.204380

BACKGROUND: A complex of Zn and carnosine, called Zinc-L-carnosine (ZnC), enjoys a wide application as part of a Zn supplement therapeutic method as well as in treating peptic ulcers. However, researches fail to confirm the biological functions possessed by ZnC as well as tumor immune microenvironment in colorectal cancer (CRC).
METHODS: Cell counting kit 8(CCK8), 5-ethynyl-2'-deoxyuridine (EdU), transwell and wound healing assays were conducted to study the influence of ZnC in the proliferating, invading and migrating processes of CRC cell lines (HCT116, LOVO) in vitro. The antitumor activity ZnC as well as its effects on tumor immune microenvironment were then assessed using CRC subcutaneous tumors in the C57BL/6 mouse model.
RESULTS: According to CCK8, EdU, transwell and wound healing assays, ZnC inhibited CRC cell lines in terms of proliferation, invasion and migration. ZnC could inhibit miR-570 for up-regulating PD-L1 expression. In vivo experiments showed that gavage (100 mg/kg, once every day) of ZnC inhibited the tumor growth of CRC, and the combination of ZnC and anti-PD1 therapy significantly improved the efficacy exhibited by anti-PD1 in treating CRC. In addition, mass cytometry results showed that immunosuppressive cells including regulatory T cells (tregs), bone marrow-derived suppressor cells (MDSC), and M2 macrophages decreased whereas CD8+ T cells elevated after adding ZnC.
CONCLUSIONS: The present study reveals that ZnC slows the progression of CRC by inhibiting CRC cells in terms of proliferation, invasion and migration, meanwhile up-regulating PD-L1 expression via inhibiting miR-570. The ZnC-anti-PD1 co-treatment assists in synergically increasing anti-tumor efficacy in CRC therapy.

Matched MeSH terms: MicroRNAs*
Fulltext 5' isomiR variation is of functional and evolutionary importance

Tan GC, Chan E, Molnar A, Sarkar R, Alexieva D, Isa IM, et al.

Nucleic Acids Res, 2014 Aug;42(14):9424-35.
PMID: 25056318 DOI: 10.1093/nar/gku656

We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3' and/or 5' end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5' differences and in support of this we report that a 5' isomiR-9-1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5' isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes.

Matched MeSH terms: MicroRNAs/genetics; MicroRNAs/metabolism*; MicroRNAs/chemistry
Fulltext Circulatory microRNA-145 expression is increased in cerebral ischemia

Gan CS, Wang CW, Tan KS

Genet. Mol. Res., 2012;11(1):147-52.
PMID: 22370881 DOI: 10.4238/2012.January.27.1

Cerebral ischemia or ischemic stroke is mainly attributed to vascular and circulation disorders. Among protein biomarkers, RNA profiles have also been identified as markers of ischemic stroke. MicroRNA-145 expression is ostensibly recognized as marker and modulator of vascular smooth muscle cell phenotype; however, expression levels in ischemic stroke had not been investigated. Employing real-time quantitative PCR, we examined the expression profile of circulatory microRNA-145 in healthy control subjects (N = 14) and ischemic stroke patients (N = 32). Circulatory microRNA-145 expression was significantly higher in ischemic stroke patients than in control subjects. This demonstrates that hemostatic mechanisms are affected by ischemic stroke. We conclude that circulating microRNA-145 has potential as a biomarker for ischemic stroke.

Matched MeSH terms: MicroRNAs/blood*; MicroRNAs/genetics; MicroRNAs/metabolism*
Fulltext MicroRNA 299-3p modulates replicative senescence in endothelial cells

Jong HL, Mustafa MR, Vanhoutte PM, AbuBakar S, Wong PF

Physiol Genomics, 2013 Apr 1;45(7):256-67.
PMID: 23362143 DOI: 10.1152/physiolgenomics.00071.2012

MicroRNAs (miRNAs) regulate various cellular processes. While several genes associated with replicative senescence have been described in endothelial cells, miRNAs that regulate these genes remain largely unknown. The present study was designed to identify miRNAs associated with replicative senescence and their target genes in human umbilical vein endothelial cells (HUVECs). An integrated miRNA and gene profiling approach revealed that hsa-miR-299-3p is upregulated in senescent HUVECs compared with the young cells, and one of its target genes could be IGF1. IGF1 was upregulated in senescent compared with young HUVECs, and knockdown of hsa-miR-299-3p dose-dependently increased the mRNA expression of IGF1, more significantly observed in the presenescent cells (passage 19) compared with the senescent cells (passage 25). Knockdown of hsa-miR-299-3p also resulted in significant reduction in the percentage of cells positively stained for senescence-associated β-galactosidase and increases in cell viability measured by MTT assay but marginal increases in cell proliferation and cell migration capacity measured by real-time growth kinetics analysis. Moreover, knockdown of hsa-miR-299-3p also increased proliferation of cells treated with H2O2 to induce senescence. These findings suggest that hsa-miR-299-3p may delay or protect against replicative senescence by improving the metabolic activity of the senesced cells but does not stimulate growth of the remaining cells in senescent cultures. Hence, these findings provide an early insight into the role of hsa-miR-299-3p in the modulation of replicative senescence in HUVECs.

Matched MeSH terms: MicroRNAs/antagonists & inhibitors; MicroRNAs/genetics; MicroRNAs/metabolism; MicroRNAs/physiology*
MicroRNA pathways: an emerging role in identification of therapeutic strategies

Vijayarathna S, Oon CE, Jothy SL, Chen Y, Kanwar JR, Sasidharan S

Curr Gene Ther, 2014;14(2):112-20.
PMID: 24588707

For years researchers have exerted every effort to improve the influential roles of microRNA (miRNA) in regulating genes that direct mammalian cell development and function. In spite of numerous advancements, many facets of miRNA generation remain unresolved due to the perplexing regulatory networks. The biogenesis of miRNA, eminently endures as a mystery as no universal pathway defines or explicates the variegation in the rise of miRNAs. Early evidence in biogenesis ignited specific steps of being omitted or replaced that eventuate in the individual miRNAs of different mechanisms. Understanding the basic foundation concerning how miRNAs are generated and function will help with diagnostic tools and therapeutic strategies. This review encompasses the canonical and the non-canonical pathways involved in miRNA biogenesis, while elucidating how miRNAs regulate genes at the nuclear level and also the mechanism that lies behind circulating miRNAs.

Matched MeSH terms: MicroRNAs/genetics*
MicroRNA-based Biosensors for Early Detection of Cancers

Rezayi M, Farjami Z, Hosseini ZS, Ebrahimi N, Abouzari-Lotf E

Curr Pharm Des, 2018;24(39):4675-4680.
PMID: 30636591 DOI: 10.2174/1381612825666190111144525

Small noncoding microRNAs (miRNAs) are known as noninvasive biomarkers for early detection in various cancers. In fact, miRNAs have key roles in carcinogenicity process such as proliferation, apoptosis and metastasis. After cardiovascular disease, cancer is the second cause of death in the world with an estimated 9.6 million deaths in 2018. So, early diagnosis of cancer is critical for successful treatment. To date, several selective and sensitive laboratory-based methods have been applied for the detection of circulating miRNA, but a simple, short assay time and low-cost method such as a biosensor method as an alternative approach to monitor cancer biomarker is required. In this review, we have highlighted recent advances in biosensors for circulating miRNA detection.

Matched MeSH terms: MicroRNAs/blood*

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