scholarly journals MicroRNAs as Potential Biomarkers in Cancer: Opportunities and Challenges

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Huiyin Lan ◽  
Haiqi Lu ◽  
Xian Wang ◽  
Hongchuan Jin

MicroRNAs (miRNAs) are a group of small noncoding RNAs (ncRNAs) that posttranscriptionally regulate gene expression by targeting their corresponding messenger RNAs (mRNAs). Dysregulated miRNAs have been considered as a new type of ‘‘oncomiRs’’ or ‘‘tumor suppressors,” playing essential roles in cancer initiation and progression. Using genome-wide detection methods, ubiquitously aberrant expression profiles of miRNAs have been identified in a broad array of human cancers, showing great potential as novel diagnostic and prognostic biomarkers of cancer with high specificity and sensitivity. The detectable miRNAs in tissue, blood, and other body fluids with high stability provide an abundant source for miRNA-based biomarkers in human cancers. Despite the fact that an increasing number of potential miRNA biomarkers have been reported, the transition of miRNAs-based biomarkers from bench to bedside still necessitates addressing several challenges. In this review, we will summarize our current understanding of miRNAs as potential biomarkers in human cancers.

Micromachines ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 1409
Author(s):  
Sze Shin Low ◽  
Daizong Ji ◽  
Wai Siong Chai ◽  
Jingjing Liu ◽  
Kuan Shiong Khoo ◽  
...  

MicroRNAs (miRNAs) are important non-coding, single-stranded RNAs possessing crucial regulating roles in human body. Therefore, miRNAs have received extensive attention from various disciplines as the aberrant expression of miRNAs are tightly related to different types of diseases. Furthermore, the exceptional stability of miRNAs has presented them as biomarker with high specificity and sensitivity. However, small size, high sequence similarity, low abundance of miRNAs impose difficulty in their detection. Hence, it is of utmost importance to develop accurate and sensitive method for miRNA biosensing. Electrochemical biosensors have been demonstrated as promising solution for miRNA detection as they are highly sensitive, facile, and low-cost with ease of miniaturization. The incorporation of nanomaterials to electrochemical biosensor offers excellent prospects for converting biological recognition events to electronic signal for the development of biosensing platform with desired sensing properties due to their unique properties. This review introduces the signal amplification strategies employed in miRNA electrochemical biosensor and presents the feasibility of different strategies. The recent advances in nanomaterial-based electrochemical biosensor for the detection of miRNA were also discussed and summarized based on different types of miRNAs, opening new approaches in biological analysis and early disease diagnosis. Lastly, the challenges and future prospects are discussed.


Author(s):  
Jocelyn M Cuthbert ◽  
Stewart J Russell ◽  
Irina A Polejaeva ◽  
Qinggang Meng ◽  
Kenneth L White ◽  
...  

Abstract Production of embryos with high developmental competence by somatic cell nuclear transfer (scNT) is far less efficient than for in vitro fertilized (IVF) embryos, likely due to an accumulation of errors in genome reprogramming that results in aberrant expression of RNA transcripts, including messenger RNAs (mRNA) and, possibly, microRNAs (miRNA). Thus, our objectives were to use RNAseq to determine the dynamics of mRNA expression in early developing scNT and IVF embryos in the context of the maternal-to-embryonic transition (MET) and to correlate apparent transcriptional dysregulation in cloned embryos with miRNA expression profiles. Comparisons between scNT and IVF embryos indicated large scale transcriptome differences, which were most evident at the 8-cell and morula stages for genes associated with biological functions critical for the MET. For two miRNAs previously identified as differentially expressed in scNT morulae, miR-34a and miR-345, negative correlations with some predicted mRNA targets were apparent, though not widespread among the majority of predicted targets. Moreover, although large-scale aberrations in expression of mRNAs were evident during the MET in cattle scNT embryos, these changes were not consistently correlated with aberrations in miRNA expression at the same developmental stage, suggesting that other mechanisms controlling gene expression may be involved.


2018 ◽  
Vol 19 (9) ◽  
pp. 2515 ◽  
Author(s):  
Junyun Luo ◽  
Hui Liu ◽  
Siyu Luan ◽  
Chongsheng He ◽  
Zhaoyong Li

N6-methyladenosine (m6A) is the most prevalent internal modification of eukaryotic messenger RNAs (mRNAs). The m6A modification in RNA can be catalyzed by methyltransferases, or removed by demethylases, which are termed m6A writers and erasers, respectively. Selective recognition and binding by distinct m6A reader proteins lead mRNA to divergent destinies. m6A has been reported to influence almost every stage of mRNA metabolism and to regulate multiple biological processes. Accumulating evidence strongly supports the correlation between aberrant cellular m6A level and cancer. We summarize here that deregulation of m6A modification, resulting from aberrant expression or function of m6A writers, erasers, readers or some other protein factors, is associated with carcinogenesis and cancer progression. Understanding the regulation and functional mechanism of mRNA m6A modification in cancer development may help in developing novel and efficient strategies for the diagnosis, prognosis and treatment of human cancers.


2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaonan Liu ◽  
Pei Wang ◽  
Xufei Teng ◽  
Zhang Zhang ◽  
Shuhui Song

BackgroundN6-methyladenosine (m6A), the most abundant chemical modification on eukaryotic messenger RNA (mRNA), is modulated by three class of regulators namely “writers,” “erasers,” and “readers.” Increasing studies have shown that aberrant expression of m6A regulators plays broad roles in tumorigenesis and progression. However, it is largely unknown regarding the expression regulation for RNA m6A regulators in human cancers.ResultsHere we characterized the expression profiles of RNA m6A regulators in 13 cancer types with The Cancer Genome Atlas (TCGA) data. We showed that METTL14, FTO, and ALKBH5 were down-regulated in most cancers, whereas YTHDF1 and IGF2BP3 were up-regulated in 12 cancer types except for thyroid carcinoma (THCA). Survival analysis further revealed that low expression of several m6A regulators displayed longer overall survival times. Then, we analyzed microRNA (miRNA)-regulated and DNA methylation-regulated expression changes of m6A regulators in pan-cancer. In total, we identified 158 miRNAs and 58 DNA methylation probes (DMPs) involved in expression regulation for RNA m6A regulators. Furthermore, we assessed the survival significance of those regulatory pairs. Among them, 10 miRNAs and 7 DMPs may promote cancer initiation and progression; conversely, 3 miRNA/mRNA pairs in kidney renal clear cell carcinoma (KIRC) may exert tumor-suppressor function. These findings are indicative of their potential prognostic values. Finally, we validated two of those miRNA/mRNA pairs (hsa-miR-1307-3p/METTL14 and hsa-miR-204-5p/IGF2BP3) that could serve a critical role for potential clinical application in KIRC patients.ConclusionsOur findings highlighted the importance of upstream regulation (miRNA and DNA methylation) governing m6A regulators’ expression in pan-cancer. As a result, we identified several informative regulatory pairs for prognostic stratification. Thus, our study provides new insights into molecular mechanisms of m6A modification in human cancers.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lijuan Lyu ◽  
Shizhen Zhang ◽  
Yujiao Deng ◽  
Meng Wang ◽  
Xinyue Deng ◽  
...  

AbstractCircular RNAs (circRNAs) are a new class of endogenous regulatory RNAs characterized by covalently closed cyclic structure lacking poly-adenylated tails, and are capable of regulating gene expression at transcription or post-transcription levels. Recently, plentiful circRNAs have been discovered in breast cancer and some circRNAs expression profiles are specifically involved in the triple-negative breast cancer (TNBC). TNBC is a type of malignant tumor defined by the lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression. Considering its clinical characteristics of high invasion, metastasis, poor prognosis, and lack of effective response to conventional chemotherapies or targeted therapies, it could be a promosing option to discover specific circRNAs as new targets for TNBC treatment. Meanwhile, accumulating evidence has demonstrated that circRNAs are dysregulated in TNBC tissues and are correlated with clinicopathological features and prognosis of TNBC patients. Furthermore, looking for circRNAs with high specificity and sensitivity will provide a new opportunity for the early diagnosis, clinical treatment, and prognosis monitoring of TNBC. Herein, we reviewed the biogenesis, regulatory mechanisms, and biological functions of circRNAs in TNBC and summarized the relationship between circRNAs expression and the clinicopathology, diagnosis, and prognosis of patients with TNBC.


Author(s):  
T. Yu. Zagoskina ◽  
E. Yu. Markov ◽  
E. A. Chaporgina ◽  
Yu. O. Popova ◽  
T. M. Dolgova ◽  
...  

Aim. Comparison of effectiveness of solid phase methods of immune detection of botulinic toxin in blood sera of a patient with botulism diagnosis: dot-immune assay using specific anti-botulinic antibodies (AT) labeled with nanoparticles of colloid silver, phosphorescent analysis (PHOSPHAN) using streptavidin label with platinum coproporphyrin (PtCP) and polystyrene nanoparticles, containing chelate complex of europium ions with naphthoyl trifluoroacetone (NA-Eu). Materials and methods. Silver nanoparticle labeled IgG isolated from a commercial diagnostic polyvalent sera against type А, В, С, E, F botulotoxins manufactured by SPA Allergen (Stavropol) with 5000 - 10000 IU activity and biotin conjugated commercial monoclonal antibodies against botulotoxin A, polyclonal mono-specific AB against botulotixin В and E and polyvalent immunoglobulin against botulotoxin А, В, С, E, F. Detection ofbotulotoxin in clinical material was carried out in dot-immunoassay on nitrocellulose membrane by PHOSPHAN method in an experimental test system using 2 detector systems based on streptavidin: PtCP and NA-Eu. Results. Botulotoxin was detected in blood sera of the botulism patient using both of the developed immune detection methods. PHOSPHAN method allowed to identify serotype В botulotoxin, that corresponded with the results obtained in botulotoxin biological neutralization reaction. Sensitivity of PHOSPHAN with NA-Eu luminescent nanoparticle based detection system was higher than with PtCP label. Conclusion. The developed methods (PHOSPHAN and dot-immunoassay) differ by high specificity and sensitivity and may be recommended for express detection of botulinic toxin in clinical material.


2021 ◽  
Vol 18 (4) ◽  
pp. 745-754
Author(s):  
Nguyen Truong Giang ◽  
Tran Thi Bich Dao ◽  
Le Quang Huan ◽  
La Thi Huyen

Antibiotics used in livestock production offer various benefits as an antimicrobial agent, growth promoter, and feed effective improvement. However, the abuse of antibiotics leads to antibiotic resistance which may seriously threaten human and animal welfare, and growing levels of antibiotics or antibiotic-resistant bacteria in the environment increase the numbers of drug-resistant infection outbreaks. Therefore, many detection methods have been being developed to quickly assess antibiotic content and its residues in foods. Among many analytical methods, the aptamer-based biosensor has considerable attention for its outstanding advantages such as high specificity, high sensitivity, and good selectivity. We use the ELAA (Enzyme-Linked Aptamer Assay) method - a variant of ELISA - which has a high affinity with neomycin. Firstly, we investigated different buffers to create the Neo-BSA complex. As result, 2-(N-morpholino) ethanesulfonic acid (MES) buffer pH 7 was found with the best results. Next, to help the Neo-BSA complex be fixed well on polystyrene wells, we surveyed various buffers and found the coating buffer (50mM Bicarbonate buffer, pH 9.6) rated as the most suitable for this process. In addition, the quality of the kit is also assessed through competitive ELAA reaction components. Therefore, we have investigated and optimized conditions such as aptamer concentration 25 nM in PBS buffer, and the biotinized aptamers did not need heat treatment prior to joining the reaction. From the results, we have successfully developed a calibration curve for antibiotic residue in milk using the ELAA technique, linear range 0,1 ng/mL and 100 ng/mL. Then, we initially surveyed 20 milk samples found that the ELAA method was consistent with the results from LC-MS/MS was obtained showing no difference between the two methods. We continued to test the samples to determine the kit’s sensitivity and specificity. The results showed that the kit has a specificity and sensitivity of 100%. Finally, LOD and LOQ value had xavg = 0.448; SD = 0.22, LOD = xavg + 3SD = 1.11 (ng / ml); LOQ = x tb + 10SD = 2.65 (ng / mL). We will continue to optimize the kit before being brought to the market.


Folia Medica ◽  
2016 ◽  
Vol 57 (3-4) ◽  
pp. 159-172 ◽  
Author(s):  
Tatyana M. Kichukova ◽  
Nikolay T. Popov ◽  
Hristo Y. Ivanov ◽  
Tihomir I. Vachev

AbstractNeuropsychiatric diseases, such as schizophrenia, bipolar disorder (BD), major depressive disorder (MDD) and autism spectrum disorder (ASD), are a huge burden on society, impairing the health of those affected, as well as their ability to learn and work. Biomarkers that reflect the dysregulations linked to neuropsychiatric diseases may potentially assist the diagnosis of these disorders. Most of these biomarkers are found in the brain tissue, which is not easily accessible. This is the challenge for the search of novel biomarkers that are present in various body fluids, including serum or plasma. As a group of important endogenous small noncoding RNAs that regulate gene expression at post-transcriptional level, microRNAs (miRNAs) play a crucial role in many physiological and pathological processes. Previously, researchers discovered that miRNAs contribute to the neurodevelopment and maturation, including neurite outgrowth, dendritogenesis and dendritic spine formation. These developments underline the significance of miRNAs as potential biomarkers for diagnosing and prognosing central nervous system diseases. Accumulated evidence indicates that there are considerable differences between the cell-free miRNA expression profiles of healthy subjects and those of patients. Therefore, circulating miRNAs are likely to become a new class of noninvasive, sensitive biomarkers. Despite the fact that little is known about the origin and functions of circulating miRNAs, their essential roles in the clinical diagnosis and prognosis of neuropsychiatric diseases make them attractive biomarkers. In this review we cover the increasing amounts of dataset that have accumulated in the last years on the use of circulating miRNAs and their values as potential biomarkers in most areas of neuropsychiatric diseases.


2020 ◽  
Vol 20 (10) ◽  
pp. 831-840
Author(s):  
Weibin Li

Sepsis is still a severe health problem worldwide with high morbidity and mortality. Blood bacterial culture remains the gold standard for the detection of pathogenic bacteria in bloodstream infections, but it is time-consuming, and both the sophisticated equipment and well-trained personnel are required. Immunoassays and genetic diagnosis are expensive and limited to specificity and sensitivity. Aptamers are single-stranded deoxyribonucleic acid (ssDNA) and ribonucleic acid (RNA) oligonucleotide or peptide sequence generated in vitro based on the binding affinity of aptamer-target by a process known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX). By taking several advantages over monoclonal antibodies and other conventional small-molecule therapeutics, such as high specificity and affinity, negligible batch-to-batch variation, flexible modification and production, thermal stability, low immunogenicity and lack of toxicity, aptamers are presently becoming promising novel diagnostic and therapeutic agents. This review describes the prospective application of aptamerbased laboratory diagnostic assays and therapeutics for pathogenic bacteria and toxins in bloodstream infections.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ping Yan ◽  
Zuotian Huang ◽  
Tong Mou ◽  
Yunhai Luo ◽  
Yanyao Liu ◽  
...  

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common and deadly malignant tumors, with a high rate of recurrence worldwide. This study aimed to investigate the mechanism underlying the progression of HCC and to identify recurrence-related biomarkers. Methods We first analyzed 132 HCC patients with paired tumor and adjacent normal tissue samples from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). The expression profiles and clinical information of 372 HCC patients from The Cancer Genome Atlas (TCGA) database were next analyzed to further validate the DEGs, construct competing endogenous RNA (ceRNA) networks and discover the prognostic genes associated with recurrence. Finally, several recurrence-related genes were evaluated in two external cohorts, consisting of fifty-two and forty-nine HCC patients, respectively. Results With the comprehensive strategies of data mining, two potential interactive ceRNA networks were constructed based on the competitive relationships of the ceRNA hypothesis. The ‘upregulated’ ceRNA network consists of 6 upregulated lncRNAs, 3 downregulated miRNAs and 5 upregulated mRNAs, and the ‘downregulated’ network includes 4 downregulated lncRNAs, 12 upregulated miRNAs and 67 downregulated mRNAs. Survival analysis of the genes in the ceRNA networks demonstrated that 20 mRNAs were significantly associated with recurrence-free survival (RFS). Based on the prognostic mRNAs, a four-gene signature (ADH4, DNASE1L3, HGFAC and MELK) was established with the least absolute shrinkage and selection operator (LASSO) algorithm to predict the RFS of HCC patients, the performance of which was evaluated by receiver operating characteristic curves. The signature was also validated in two external cohort and displayed effective discrimination and prediction for the RFS of HCC patients. Conclusions In conclusion, the present study elucidated the underlying mechanisms of tumorigenesis and progression, provided two visualized ceRNA networks and successfully identified several potential biomarkers for HCC recurrence prediction and targeted therapies.


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