Evaluation of plasma exosomal miR-214-3p as a potential biomarker for diagnosis and prognosis of uveal melanoma / 中华实验眼科杂志

Objective:To investigate the differential expression of microRNA (miR)-214-3p in plasma exosomes in different types of uveal melanoma (UM) and evaluate whether miR-214-3p is a potential molecular biomarker for the diagnosis and prognosis of UM.Methods:Twenty-five UM in situ patients who received the enucleation of eyeball were enrolled at Beijing Tongren Hospital from December 2015 to October 2019, including 10 with epithelioid cell melanoma and 10 with spindle cell melanoma as well as 5 metastatic UM patients (1 with spindle cell-like melanoma and 4 with epithelioid cell-like melanoma) and 10 healthy subjects were enrolled during the same period.Blood sample was collected from all the subjects for the isolation of plasma exosomes.The morphology of exosomes was examined under the electron microscope.The exsomal marker proteins were identified by Western blot.The expression level of miR-214-3p in plasma exosomes was detected by real-time fluorescence quantitative PCR.The differential expression of miR-214-3p among different types of UM patients and healthy controls was compared.The diagnostic and classification performance of exosomal miR-214-3p was evaluated using receiver operating characteristic curve.Written informed consent was obtained from each subject prior to entering the study cohort.This study protocol was approved by an Ethics Committee of Capital Medical Univeristy (No.TRECKY2018-056).Results:The isolated exosomes were hemispherical in shape with a concavity on one side.The diameter of the exosomes was about 100 nm and the particle diameter of vesicles from samples was (82.0±2.7) nm.TSG101 protein was detectable and Calnexin protein was not found in the exosomes.The relative expression levels of plasma exosomal miR-214-3p in healthy control group, in situ UM group and metastatic UM group were 0.86(0.57, 1.49), 0.24(0.10, 0.67), and 0.43(0.23, 0.56), respectively.The miR-214-3p relative expression level in plasma exosomes of in situ UM patients and metastatic UM patients was significantly lower than that of healthy controls, and the differences were statistically significant ( Z=2.62, P<0.01; Z=2.08, P<0.05). The relative expression levels of exosomal miR-214-3p in spindle cell-like UM group and epithelioid cell-like UM group were 0.11(0.07, 0.64) and 0.46(0.14, 0.91), respectively, and no significant difference was found in the expression level of plasma exosomal miR-214-3p among different types of UM (all at P>0.05). The area under the curve of plasma exosomal miR-214-3p for UM diagnosis was 0.795. Conclusions:Plasma exosomal miR-214-3p level is significantly reduced in both in situ UM patients and metastatic UM patients.Plasma exosomal miR-214-3p is a new potential diagnostic biomarker for UM, but the exosomal miR-214-3p appears to not be able to distinguish the types of UM.

Role of microRNA in complications of offspring born to mothers with gestational diabetes mellitus / 中华围产医学杂志

Gestational diabetes mellitus (GDM) can lead to adverse pregnancy outcomes and epigenetic changes in offspring due to exposure to a high-glucose intrauterine environment, resulting in related short- and long-term complications. MicroRNA (miRNA)-mediated post-transcriptional regulation, a gene expression regulation mechanism that has gained much attention in recent years, may play a role in morbidity in offspring born to mothers with GDM, such as macrosomia, heart development, neurodevelopment, and long-term metabolic diseases. This article reviews the progress of miRNA in GDM and associated complications in the offspring.

Diagnostic potential of circulating microRNA in vascular cognitive impairment / 中国组织工程研究

BACKGROUND: To date, vascular cognitive impairment (VCI) still lacks effective therapeutic strategy and objective diagnostic tool. Circulating microRNA is considered as a promising diagnostic biomarker due to its advantages of easy acquisition, non-invasive collection, easy detection, strong specificity, and stable expression. OBJECTIVE: To review domestic and foreign studies of microRNAs in VCI diagnosis. METHODS: Literatures published from January 2009 to January 2020 were searched in PubMed, Web of Science, Scopus, Embase, OVID, CNKI and WanFang databases with keywords of “microRNA, vascular cognitive impairment, post-stroke cognitive impairment, diagnosis, biomarker ” in English and Chinese, respectively. Finally, 42 literatures were included for analysis. RESULTS AND CONCLUSION: Compared with the normal cognitive population, differentially expressed microRNAs are found in the serum, plasma and cerebrospinal fluid of VCI patients, and the expression levels of some microRNAs are correlated with the cognitive assessment score. Taking together, circulating microRNA is a new biomarker with potential diagnostic value for VCI. However, the clinical application of microRNAs in VCI still has a large room for development due to the small sample size and low specificity or sensitivity of candidate microRNAs.

Research of peripheral blood non-coding RNA in diagnosis of breast cancer / 中华检验医学杂志

A large amount of non-coding RNA are found existing in eukaryotic transcriptome, which play an important role in regulating the expression of genes as well as participating in physiological and pathological process of various cells.In recent years,the research of ncRNA in diagnosis of breast cancer is extremely hot. In this review, the research of three types of peripheral blood ncRNAs as breast cancer diagnostic biomarkers were reviewed, including microRNA(miRNA), long non-coding RNA(lncRNA), and circular RNA(circRNA).Also,the prospect of ncRNA in clinical research and translational medicine of breast cancer was mentioned, in order to provide a new idea for breast cancer with the discovery of diagnostic markers in early detection and the monitoring of diagnosis and treatment process.

Research of peripheral blood non-coding RNA in diagnosis of breast cancer / 中华检验医学杂志

A large amount of non-coding RNA are found existing in eukaryotic transcriptome, which play an important role in regulating the expression of genes as well as participating in physiological and pathological process of various cells.In recent years,the research of ncRNA in diagnosis of breast cancer is extremely hot. In this review, the research of three types of peripheral blood ncRNAs as breast cancer diagnostic biomarkers were reviewed, including microRNA(miRNA), long non-coding RNA(lncRNA), and circular RNA(circRNA).Also,the prospect of ncRNA in clinical research and translational medicine of breast cancer was mentioned, in order to provide a new idea for breast cancer with the discovery of diagnostic markers in early detection and the monitoring of diagnosis and treatment process.

Circulating Cell-free Tumor Nucleic Acids in Gastric Cancer

Gastric cancer is still the leading cause of cancer deaths, especially in Asian countries. Recently, many studies have analyzed cell-free nucleic acids (cfNAs) circulating in the blood, for the early diagnosis of cancer and monitoring its progression. Circulating tumor nucleic acids (ctNAs) originate in a tumor and contain tumor-related genetic or epigenetic alterations. This review defines the nomenclatures of each form of cfNAs and describes the characteristics of circulating tumor DNA (ctDNA) and microRNA (miRNA), two major forms of ctNAs studied in gastric cancer research to date. We compare available studies on ctDNA, and explain trends observed in studies of miRNAs in gastric cancers. As these new blood-based biomarkers have attracted increasing attention, we have discussed several important points to be considered before the clinical translation of ctNA detection. We have also discussed the current status of research in this field, and clinical applications of specific ctNAs as tumor markers for gastric cancer diagnosis.

Altered expression and clinical significance of plasma circulating microRNA-23b in patients with myasthnia gravis / 中华神经科杂志

Objective To evaluate the expression and clinical significance of plasma circulating microRNA-23b in patients with myasthenia gravis (MG).Methods Plasma samples from 32 MG patients and 32 healthy people were collected in the Second Affiliated Hospital of Harbin Medical University from October 2015 to August 2016. Expression of microRNA-23b was detected by quantitative reverse transcription polymerase chain reaction .The relationship among microRNA-23b expression level, clinical features and quantitative myasthenia gravis score ( QMG ) was analyzed. Results The expression of circulating microRNA-23b in plasma was significantly higher in MG patients (4.587 (3.654, 5.423)) compared with control group (2.889 (1.968, 4.027), Z=-4.169, P<0.01), meanwhile it was positively related to QMG (r=0.661,P<0.01).But the expression of circulating microRNA-23b had no statistically significant difference in MG subgroups .Conclusion Plasma circulating microRNA-23b is highly expressed in MG and has positive correlation with MG severity .

Low Expression of Circulating MicroRNA-34c is Associated with Poor Prognosis in Triple-Negative Breast Cancer

PURPOSE: The microRNA-34 (miR-34) family is important in tumor regulation. This study aimed to investigate the association of circulating miR-34 family proteins with clinicopathological features and their prognostic value in triple-negative breast cancer (TNBC) patients. MATERIALS AND METHODS: In this cohort study, 173 TNBC patients admitted to First People's Hospital of Shunde from May 1, 2009 to April 30, 2013 were enrolled. Meanwhile, 75 age-matched healthy women volunteers were identified as healthy controls (HCs). We examined the expression of miR-34 family (miR-34a/b/c) proteins in plasma collected from TNBC patients before any treatment was performed and from age-matched HCs using qPCR methods. RESULTS: The expressions of miR-34a/34b/34c were significantly lower in TNBC patients than in HC (p<0.001, p=0.027, p<0.001, respectively). miR-34a was correlated with tumor grade (p=0.038), lymph node positive (p=0.027), distant metastasis (p=0.004), and surgery (p=0.023); miR-34b was correlated with lymph node positivity (p=0.027); and miR-34c was correlated with tumor grade (p=0.017) and distant metastasis (p<0.001). Kaplan-Meier curve analysis displayed low expression of miR-34a as associated with worse overall survival (OS) (p=0.011), as well as miR-34c low expression (p=0.002). In addition, univariate and multivariate Cox proportional hazards regression was performed, and low expression of miR-34c (p=0.011) was found to be an independent risk factor for OS, as well as tumor grade (p=0.013), lymph node positive (p=0.050), and distant metastasis (p=0.021). CONCLUSION: In conclusion, this study demonstrated reduced miR-34a/c expression is highly associated with tumor progression and indicated worse prognosis. Also, miR-34c was an independent risk factor for OS in TNBC patients.

Circulating microRNAs as potential cancer biomarkers / MicroRNA circulantes como potenciales biomarcadores en cáncer

Cancer is currently recognized as a major cause of mortality worldwide, and, as such, has a significant impact on public health. Successful early detection strategies are linked to a decrease in mortality; however, because they are invasive, highly complex, and have low specificity, their application has been limited. MicroRNAs (miRNAs) are short, non-coding RNA sequences capable of regulating gene expression. Molecular mechanisms of miRNAs in cancer are not fully understood, but specific patterns of miRNAs expression have been associated with many tumour types. MicroRNAs as biomarkers can help to identify tumour origin and allow their early detection. They can also be used to monitor progression and therapeutic response. The presence and stability of miRNAs in blood, as circulating miRNAs, are major factors that contribute to their use as potential biomarkers in a clinical context. The aim of this article is to present a review of miRNAs as circulating biomarkers in cancer.

El cáncer es reconocido como una de las principales causas de mortalidad a nivel mundial teniendo así un impacto significativo en la salud pública. Una disminución en la mortalidad por esta enfermedad se ha asociado con estrategias exitosas de detección temprana; sin embargo, debido a que estas son invasivas, altamente complejas y registran baja especificidad, su aplicación ha sido limitada. Los microRNA (miRNA) son RNA no codificantes de secuencias cortas, capaces de regular la expresión génica. Los mecanismos moleculares de los miRNA en cáncer aún no están totalmente clarificados, pero patrones específicos de la expresión de estos han sido asociados con muchos tipos de tumores. Los miRNA como biomarcadores pueden ayudar a identificar el origen de un tumor, realizar detección temprana, predecir la progresión de la enfermedad y la respuesta al tratamiento. La presencia y estabilidad de los miRNA en la sangre, como miRNA circulantes, son los principales factores que contribuyen a su uso potencial como biomarcadores en un contexto clínico. El objetivo de este artículo es realizar una revisión sobre los miRNA circulantes en cáncer.

Circulating miR-106a in serum are potential biomarker for renal cell carcinoma / 中华泌尿外科杂志

Objective To detect the circulating miR-106a levels in serum before and after surgery in patients with renal clear cell carcinoma,and to explore its relationship with clinical-pathological parameters.Methods 30 serum samples from patients with renal clear cell carcinoma were collected before and after surgery during February 2013 to July 2014.This study included 30 normal controls.All serum miR-106a levels were detected using the real-time PCR.Results The serum miR-l06a levels in patients with renal clear cell carcinoma pre-operatively wcre significantly greater than normal controls (Z =-4.251,P =0.0001).The serum miR-106a levels in patients post-operatively had no significant differences compared to normal controls (Z =-0.244,P =0.807).The serum miR-106a levels in post-operative samples were significantly lower than the pre-operative samples (Z =-4.229,P =0.0001).Serum miR-106a levels and other clinical-pathological parameters had no correlation in patients with renal clear cell carcinoma(tumor size:Z =-0.775,P =0.439;Fuhrman grade:Z =-1.694,P =0.090).The receiver operating characteristic curve was used to distinguish pre-operative samples and normal controls,its AUC was 0.819 (95％ CI:0.710-0.929,P =0.0001) with 86.7％ sensitivity and 70.0％ specificity.Conclusions The serum miR-106a levels in patients with renal clear cell carcinoma pre-operatively were significantly greater than post-operatively with no correlation in tumor size and Fuhrman grade.The outcome suggested that serum miR-106a can be regarded as a potential molecular marker in renal clear cell carcinoma.

Aberrant expression of circulating microRNAs in pancreatic cancer patients and in patients with gemcitabine resistance / 国际外科学杂志

Objective To investigate the differentially expressed circulating microRNAs of pancreatic cancer,and of the pancreatic cancer with gemcitabine resistance,to find potential biomarkers for noninvasive diagnosis of pancreatic cancer and the prediction of prognosis of gemcitabine.Methods To screen the highly deregulated microRNAs in the plasma samples of pancreatic cancer,and in the plasma samples ofpancreatic cancer patients with gemcitabine resistance using reverse transcription and quantitative PCR.Results Twenty-eight microRNAs expressing differentially with fold-exchange ＞ 2 was screened out comparing pancreatic cancer and healthy controls,and 28 microRNAs was screened out comparing gemcitabine resistant patients and gemcitabine positive patients.Conclusions There is a specific circulating mIcroRNA profile in pancreatic cancer as well as in pancreatic cancer with gemcitabine resistance.These profiles may have potential in noninvasive diagnosis of pancreatic cancer and the prediction of prognosis of gemcitabine.

The preliminary analysis of peripheral blood circulating microRNA expression profile in patients with ischemic and hemorrhagic stroke / 实用医学杂志

Objective To explore the peripheral blood circulating microRNA expression profile of ischemic and hemorrhagic stroke patients by using microRNA array. Methods The whole blood of 3 patients with acute ischemic stroke, 3 patients with cerebral hemorrhage and 3 healthy volunteers were collected for whole blood RNA through Norgen exosome isolation kit, and then underwent quality and density measurement through PCR. The miRNAs expression profile was studied through μParaflorTM microRNA. All the data were analyzed by associated software and statistics methods. Results 8 miRNAs associated with cerebral stroke in ischemia stroke patients and cerebral hemorrhage patients were discovered, and showed significant difference (P 0.05). Conclusions Different expression profiles of miRNA between ischemic stroke patients and hemorrhagic stroke patients may provide insights into their roles in the pathogenesis and progression of stroke. The study of miRNA can contributes to elucidate the epigenetics molecular mechanism of acute stroke.

4-(Methylnitrosamino)-1-(3-pyridyl) -1-butanone induces circulating microRNA deregulation in early lung carcinogenesis / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To study the alteration of circulating microRNAs in 4-(methylnitrosamino)-1-(3-pyridyl) -1-butanone (NNK)-induced early stage lung carcinogenesis.</p><p><b>METHODS</b>A lung cancer model of male F344 rats was induced with systemic NNK and levels of 8 lung cancer-associated miRNAs in whole blood and serum of rats were measured by quantitative RT-PCR of each at weeks 1, 5, 10, and 20 following NNK treatment.</p><p><b>RESULTS</b>No lung cancer was detected in control group and NNK treatment group at week 20 following NNK treatment. The levels of some circulating miRNAs were significantly higher in NNK treatment group than in control group. The miR-210 was down-regulated and the miR-206 was up-regulated in NNK treatment group. The expression level of circulating miRNAs changed from week 1 to week 20 following NNK treatment.</p><p><b>CONCLUSION</b>The expression level of circulating miRNAs is related to NNK-induced early stage lung carcinogenesis in rats and can therefore serve as its potential indicator.</p>

Research progress of circulating microRNA as a new biomarker of cancer / 肿瘤研究与临床

Cancer is one of the most dangerous diseases that threaten human health.The early diagnosis individual treatment and accurate judgement of recurrence play important roles in prognosis.microRNA (miRNA) is a class of small fragments of RNA molecules which has the ability to regulate the gene expression.In recent years,some researchers have begun to focus on it.Studies have shown that the great stability of circulating miRNA in body fluid,as well as the specificity in many types of cancer,which may be important for the diagnosis and prognosis of cancer patients.In this review,the advantages and limitations of circulating miRNA as a new biomarker of cancer are birfly summarized.

Circulating microRNA in colorectal cancer / 国际肿瘤学杂志

In coloreetal cancer,there are multiple abnormally expressed microRNA (miRNA),suggesting that the miRNA may be involved in tumor development process.Recently,more and more evidence shows that miRNA are more stable in the blood,compared with mRNA,which makes circulating miRNA are helpful to become the non-invasive tumor marker for the diagnosis,treatment and prognosis evaluation in coloreetal cancer.

MicroRNA, circulating microRNA and tumor / 第二军医大学学报

MicroRNAs (miRNAs) are a group of endogenous non-coding small RNA molecules of 21-25 nt. They can regulate gene expression at the transcriptional level through interaction with inhibition of target gene translation, participating in a variety of important biological processes. Increasing studies have found that miRNA plays a very important role in the development and progression of tumor, and that several miRNAs are closely related to the development of some tumors. Not only the miRNAs in the tissue, but also those in the peripheral blood are involved in the tumorigenesis, and they may be taken as biomarkers for diagnosis of patients, casting new lights on the early diagnosis in clinical practice. Detection of tumor-specific miRNAs in the blood is of great importance for the early diagnosis of tumors.