MicroRNA-195-5p suppresses glucose uptake and proliferation of human bladder cancer T24 cells by regulating GLUT3 expression

It has been reported that expression of glucose transporter member 3 (GLUT3) is up-regulated in bladder cancers. However, the regulating mechanism remains unknown. Here, we assessed whether microRNAs (miRNAs) regulate GLUT3 expression in bladder cancers. In our study, miR-195-5p was identified to directly targeted GLUT3 3'-untranslated region (UTR) in bladder cancer T24 cells. Small interfering RNA (siRNA)- and miR-195-5p-mediated GLUT3 knockdown experiments revealed that miR-195-5p decreased T24 cells glucose uptake, inhibited cell growth and promoted cell apoptosis through suppression of GLUT3 expression. Therefore, miR-195-5p is a novel and also the first identified miRNA that targets GLUT3, and the aberrant decreased expression of miR-195-5p and consequent GLUT3 up-regulation may contribute to bladder carcinogenesis.     

Mirna expression profiles identify drivers in colorectal and pancreatic cancers

Background and Aim

Altered expression of microRNAs (miRNAs) hallmarks many cancer types. The study of the associations of miRNA expression profile and cancer phenotype could help identify the links between deregulation of miRNA expression and oncogenic pathways.

Methods

Expression profiling of 866 human miRNAs in 19 colorectal and 17 pancreatic cancers and in matched adjacent normal tissues was investigated. Classical paired t-test and random forest analyses were applied to identify miRNAs associated with tissue-specific tumors. Network analysis based on a computational approach to mine associations between cancer types and miRNAs was performed.

Results

The merge between the two statistical methods used to intersect the miRNAs differentially expressed in colon and pancreatic cancers allowed the identification of cancer-specific miRNA alterations. By miRNA-network analysis, tissue-specific patterns of miRNA deregulation were traced: the driving miRNAs were miR-195, miR-1280, miR-140-3p and miR-1246 in colorectal tumors, and miR-103, miR-23a and miR-15b in pancreatic cancers.

Conclusion

MiRNA expression profiles may identify cancer-specific signatures and potentially useful biomarkers for the diagnosis of tissue specific cancers. miRNA-network analysis help identify altered miRNA regulatory networks that could play a role in tumor pathogenesis.     

Differential MicroRNAs Expression in Serum of Patients with Lung Cancer, Pulmonary Tuberculosis, and Pneumonia

MicroRNAs (miRNAs) play critical regulatory roles in the physiological and pathological processes. The high stability of miRNAs in human serum represents attractive novel diagnostic biomarkers of clinical conditions. Several studies have shown that aberrant expression of miRNAs in human cancer including lung cancer, but little is known about their effects on some infectious lung diseases such as pulmonary tuberculosis (TB) and pneumonia. In this study, we investigated miRNA expression pattern in serum of Egyptian patients with lung cancer, TB, and pneumonia compared with matched healthy controls. Using microarray-based expression profiling followed by real-time quantitative polymerase chain reaction validation, we compared the levels of a series of circulating miRNAs (miR-21, miR-155, miR-182, and miR-197) in serum from patients with lung cancer (n = 65), pulmonary tuberculosis (n = 29), pneumonia (n = 29), and transudate (n = 16) compared with matched healthy controls (n = 37). MiRNA SNORD68 was the housekeeping endogenous control. We found that the serum levels of miR-21, miR-155, and miR-197 were significantly elevated in the patients with lung cancer and pneumonia whereas miR-182 and miR-197 levels were increased only in patients with lung cancer and TB, respectively, compared with controls. Receiver operating characteristic analysis revealed that miR-182, miR-155, and miR-197 have superior diagnostic potential in discriminating patients with lung cancer, pneumonia, and TB, respectively, from controls. Our results conclude that the differential expression of the four studied miRNAs can be potential non-invasive biomarkers for patients with lung cancer, TB and pneumonia.     

Identification of mouse serum miRNA endogenous references by global gene expression profiles

MicroRNAs (miRNAs) are recently discovered small non-coding RNAs and can serve as serum biomarkers for disease diagnosis and prognoses. Lack of reliable serum miRNA endogenous references for normalization in miRNA gene expression makes single miRNA assays inaccurate. Using TaqMan® real-time PCR miRNA arrays with a global gene expression normalization strategy, we have analyzed serum miRNA expression profiles of 20 female mice of NOD/ShiLtJ (n = 8), NOR/LtJ (n = 6), and C57BL/6J (n = 6) at different ages and disease conditions. We identified five miRNAs, miR-146a, miR-16, miR-195, miR-30e and miR-744, to be stably expressed in all strains, which could serve as mouse serum miRNA endogenous references for single assay experiments.     

Profiles of serum microRNAs; miR-125b-5p and miR223-3p serve as novel biomarkers for HBV-positive hepatocellular carcinoma

Recently, circulating miRNAs have been reported as promising biomarkers for various pathologic conditions including cancer. Certain microRNAs (miRNAs) have been shown early diagnostic potential for many types of cancer. The objective of this study was to investigate the potential of certain serum/plasma miRNAs as novel non-invasive biomarkers for early diagnosis of hepatitis B virus (HBV) related hepatocellular carcinoma (HCC). For this reason, the expression levels of 24 miRNA (let-7c, miR-92a-3p, 423-5p, 150-5p, 223-3p, 125b-5p, 342-3p, miR-206, 122-5p, 375, 223-5p, 10a-5p, 23b-5p, 99a-5p, 23a-5p, 10a-3p, 122-3p, 125b-1-3p, 23b-3p, 125b-2-3p, 23a-3p, 92a-1-5p, 92a-2-5p, 99a-3p) were analyzed in plasma of patients with chronic hepatitis B, HBV-positive cirrhosis and HBV-positive HCC and compared with control group samples. Totally 94 plasma samples; 28 control and 66 patient plasma (24 CHB, 22 HBV-positive cirrhosis, 20 HBV-positive HCC) and were included in this study. The expression levels of 24 miRNAs were detected for all control and patient group plasma samples by qRT-PCR using BioMark? 96.96 Dynamic Array (Fluidigm Corporation) system. The expression levels of miR-125b-5p were detected 2.85 fold, 2.46 fold and 1.89 fold (p = 0.01513, p = 0.0009440, p = 0.0001446) up regulated in CHB, HBV-positive cirrhosis and HBV-positive HCC, respectively when compared versus control group individually by Mann–Whitney U test. The expression levels of miR-223-3p were detected 5.55 fold, 13.88 fold and 12.65 fold (p = 0.01513, p = 0.0009440, p = 0.0001446) down regulated in same comparisons. When all groups were compared versus control group by one-way ANOVA test, the expression levels of miR-223-3p were also found statistically significant (p < 0.05). Although not statistically significant, miR-125b-5p tended to be upregulated. (p = 0.07192). These results significantly imply that miR-125b-5p and miR223-3p could be used as novel non-invasive biomarkers of HBV-positive HCC in very early, even at CHB stage of liver disease.     

Systemically Circulating Viral and Tumor-Derived MicroRNAs in KSHV-Associated Malignancies

MicroRNAs (miRNAs) are stable, small non-coding RNAs that modulate many downstream target genes. Recently, circulating miRNAs have been detected in various body fluids and within exosomes, prompting their evaluation as candidate biomarkers of diseases, especially cancer. Kaposi''s sarcoma (KS) is the most common AIDS-associated cancer and remains prevalent despite Highly Active Anti-Retroviral Therapy (HAART). KS is caused by KS-associated herpesvirus (KSHV), a gamma herpesvirus also associated with Primary Effusion Lymphoma (PEL). We sought to determine the host and viral circulating miRNAs in plasma, pleural fluid or serum from patients with the KSHV-associated malignancies KS and PEL and from two mouse models of KS. Both KSHV-encoded miRNAs and host miRNAs, including members of the miR-17–92 cluster, were detectable within patient exosomes and circulating miRNA profiles from KSHV mouse models. Further characterization revealed a subset of miRNAs that seemed to be preferentially incorporated into exosomes. Gene ontology analysis of signature exosomal miRNA targets revealed several signaling pathways that are known to be important in KSHV pathogenesis. Functional analysis of endothelial cells exposed to patient-derived exosomes demonstrated enhanced cell migration and IL-6 secretion. This suggests that exosomes derived from KSHV-associated malignancies are functional and contain a distinct subset of miRNAs. These could represent candidate biomarkers of disease and may contribute to the paracrine phenotypes that are a characteristic of KS.     

Identification of a Plasma Four-microRNA Panel as Potential Noninvasive Biomarker for Osteosarcoma

Background

Circulating microRNAs (miRNAs) are emerging as promising biomarkers for human cancer. Osteosarcoma is the most common human primary malignant bone tumor in children and young adults. The objective of this study was to investigate whether circulating miRNAs in plasma could be a useful biomarker for detecting osteosarcoma and monitoring tumor removal dynamics.

Methods

Plasma samples were obtained from 90 patients before surgery, 50 patients after one month of surgery, and 90 healthy individuals. The study was divided into three steps: First, initial screening of the profiles of circulating miRNAs in pooled plasma samples from healthy controls and pre-operative osteosarcoma patients using a TaqMan low density array (TLDA). Second, evaluation of miRNA concentration in individual plasma samples from 90 pre-operative osteosarcoma patients and 90 healthy controls by a quantitative real time PCR (qRT-PCR) assay. Third, evaluation of miRNA concentration in paired plasma samples from 50 pre- and post-operative osteosarcoma patients by qRT-PCR assay.

Results

Four plasma miRNAs including miR-195-5p, miR-199a-3p, miR-320a, and miR-374a-5p were significantly increased in the osteosarcoma patients. Receiver operating characteristics curve analysis of the combined populations demonstrated that the four-miRNA signature could discriminate cases from controls with an area under the curve of 0.9608 (95% CI 0.9307-0.9912). These 4 miRNAs were markedly decreased in the plasma after operation. In addition, circulating miR-195-5p and miR-199a-3p were correlated with metastasis status, while miR-199a-3p and miR-320a were correlated with histological subtype.

Conclusions

Our data suggest that altered levels of circulating miRNAs might have great potential to serve as novel, non-invasive biomarkers for osteosarcoma.     

Dysregulated microRNAs in the pathogenesis and progression of cervical neoplasm

MicroRNAs (miRNAs) play an important role in a variety of physiological as well as pathophysiological processes, including carcinogenesis. The aim of this study is to identify a distinct miRNA expression signature for cervical intraepithelial neoplasia (CIN) and to unveil individual miRNAs that may be involved in the development of cervical carcinoma. Expression profiling using quantitative real-time RT-PCR of 202 miRNAs was performed on micro-dissected high-grade CIN (CIN 2/3) tissues and compared to normal cervical epithelium. Unsupervised hierarchical clustering of the miRNA expression pattern displayed a distinct separation between the CIN and normal cervical epithelium samples. Supervised analysis identified 12 highly differentially regulated miRNAs, including miR-518a, miR-34b, miR-34c, miR-20b, miR-338, miR-9, miR-512-5p, miR-424, miR-345, miR-10a, miR-193b and miR-203, which distinguished the high-grade CIN specimens from normal cervical epithelium. This miRNA signature was further validated by an independent set of high-grade CIN cases. The same characteristic signature can also be used to distinguish cervical squamous cell carcinoma from normal controls. Target prediction analysis revealed that these dysregulated miRNAs mainly control apoptosis signaling pathways and cell cycle regulation. These findings contribute to understanding the role of microRNAs in the pathogenesis and progression of cervical neoplasm at the molecular level.     

胃癌与癌旁组织miRNA差异表达谱的研究

目的研究胃癌中表达失调的miRNA及其生物学功能,从而进一步阐明miRNA在胃癌发生中的分子机制。方法将总RNA加ploy（A）尾后进行反转录PCR扩增特异miRNA,使用QuantityOne软件进行定量分析,计算每对样本胃癌与癌旁组织比值（T／NRatio）,使用SAM软件进行统计分析。MTT法检测miR-21和miR-17-5p对胃癌细胞系生长的影响。结果在8对胃癌及癌旁组织样本中对237个miRNA进行了表达谱分析。对于检测到表达的161个miRNA,使用SAM软件进行统计分析,确认22个在胃癌中表达上调,2个在胃癌中表达下调（FDR=0．0963）。进一步通过生长抑制试验证实在胃癌组织中表达异常增高的miR-21和miR-17-5p对胃癌细胞的生长有明显的促进作用。结论这些在胃癌中异常表达的miRNAs具有成为新一代胃癌标记物的潜力,能够为胃癌的精确诊断分型提供依据,同时针对这些靶点可以开发新的核酸治疗技术,通过抑制或增强其功能来达到治疗胃癌的目的。     

Serum microRNA expression profile as a biomarker for the diagnosis of pertussis

Pertussis is a highly contagious, respiratory disease associated with substantial morbidity and mortality. A rapid and reliable diagnostic method is essential for appropriate treatment and prevention. Expression profiles of circulating microRNAs (miRNAs) have been proven as new non-invasive biomarkers for infectious diseases. We aimed to investigated the serum miRNA profile in pertussis patients and explored its potential as a novel diagnostic biomarker for pertussis. Among 664 different miRNAs analyzed using a miRNA array, 50 were overexpressed and 81 were underexpressed in the serum of pertussis patients. Expression levels of seven candidate miRNAs were further evaluated by real-time qRT-PCR. A panel of five miRNAs (miR-202, miR-342-5p, miR-206, miR-487b, miR-576-5p) was confirmed overexpressed in pertussis patients (p < 0.05). Risk score and receiver-operating characteristic (ROC) analysis showed that the area under the curve of the five-member miRNA profile was 0.980. At an optimal cutoff value (0.707), this panel of miRNAs yielded a sensitivity of 97.4 % and a specificity of 94.3 %. These data suggest that the five-member serum miRNA profile may serve as a new biomarker for pertussis diagnosis with high specificity and sensitivity.     

Decreased miR-30b-5p expression by DNMT1 methylation regulation involved in gastric cancer metastasis

miRNAs have emerged as crucial regulators in the regulation of development as well as human diseases, especially tumorigenesis. The aims of this study are to evaluate miR-30b-5p expression pattern and mechanism in gastric carcinogenesis due to which remains to be determined. Expression of miR-30b-5p was analyzed in 51 gastric cancer cases and 4 cell lines by qRT-PCR. The effect of DNA methylation on miR-30b-5p expression was assessed by MSP and BGS. In order to know whether DNMT1 increased miR-30b-5p promoter methylation, DNMT1 was depleted in cell lines AGS and BGC-823. The role of miR-30b-5p on cell migration was evaluated by wound healing assays. Decreased expression of miR-30b-5p was found in gastric cancer samples. In tumor, the expression level of miR-30b-5p was profound correlated with lymph node metastasis (P = 0.019). The level of miR-30b-5p may be restored by DNA demethylation and DNMT1 induced miR-30b-5p promoter methylation. In vitro functional assays implied that enforced miR-30b-5p expression affected cell migration, consistent with tissues analysis. Our findings uncovered that miR-30b-5p is significantly diminished in gastric cancer tissues, providing the first insight into the epigenetic mechanism of miR-30b-5p down-regulation, induced by DNMT1, and the role of miR-30b-5p in gastric cancer carcinogenesis. Overexpression of miR-30b-5p inhibited cell migration. Thus, miR-30b-5p may represent a potential therapeutic target for gastric cancer therapy.     

Ribonucleic-acid-biomarker candidates for early-phase group detection of common cancers

Cancer is considered as a challenging lethal agent around the world and its detection at early stages would help prevention of the high mortality. Among the widely used biomarkers in clinical diagnosis of cancer, extracellular non-coding RNAs as ribonucleic acid biomarkers serve as state-of-the-art candidates for molecular diagnosis. In that regard, microRNAs are of great priority mainly because of high variety and stability in body fluids. Accordingly, common miRNAs among most prevalent cancers could help us (pre)diagnose cancer with high accuracy in target samples. In this study, common lethal cancers to humans were investigated in case of miRNA profiles to determine the possible common correlation between miRNA up-regulation or down-regulation (as a ribonucleic acid biomarker) and developing the cancers. It was shown that among the investigated miRNAs, five typical extracellular miRNAs (miR-18a, miR-21, miR-155, miR-221, and miR-375) dysregulation are predominant in most cancer varieties comprising breast, colon, lung, prostate, pancreas, gastric, ovarian, esophagus and liver. This could serve as an appropriate target site for developing point-of-care approaches for cancer detection e.g. designing diagnostic biosensor-based microarrays or kits for both quantification and qualification of the biomarkers. Besides, the miRNA candidates could be efficiently applied to cancer therapeutic approaches.     

miR-1207-5p and miR-1266 suppress gastric cancer growth and invasion by targeting telomerase reverse transcriptase

hTERT is the catalytic subunit of the telomerase complex. Elevated expression of hTERT is associated with the expansion and metastasis of gastric tumor. In this study, we aimed to identify novel tumor suppressor miRNAs that restrain hTERT expression. We began our screen for hTERT-targeting miRNAs with a miRNA microarray. miRNA candidates were further filtered by bioinformatic analysis, general expression pattern in different cell lines, gain-of-function effects on hTERT protein and the potential of these effects to suppress hTERT 3′ untranslated region (3′UTR) luciferase activity. The clinical relevance of two miRNAs (miR-1207-5p and miR-1266) was evaluated by real-time RT-PCR. The effects of these miRNAs on cell growth, cell cycle and invasion of gastric cancer cells were measured with CCK-8, flow cytometry and transwell assays. Finally, the ability of these miRNAs to suppress the transplanted tumors was also investigated. Fourteen miRNAs were identified using a combination of bioinformatics and miRNA microarray analysis. Of these fourteen miRNAs, nine were expressed at significantly lower levels in hTERT-positive cell lines compared with hTERT-negative cell lines and five could downregulate hTERT protein expression. Only miR-1207-5p and miR-1266 interacted with the 3′ UTR of hTERT and the expression levels of these two miRNAs were significantly decreased in gastric cancer tissues. These two miRNAs also inhibited gastric tumor growth in vitro and in vivo. Altogether, miR-1207-5p and miR-1266 were determined to be hTERT suppressors in gastric cancer, and the delivery of these two miRNAs represents a novel therapeutic strategy for gastric cancer treatment.     

Differential expression of miR-195 in esophageal squamous cell carcinoma and miR-195 expression inhibits tumor cell proliferation and invasion by targeting of Cdc42

MicroRNAs (miRNA) have played an important role in carcinogenesis. In this study, Agilent miRNA microarray was used to identify differentially expressed miRNAs in esophageal squamous cell carcinoma (ESCC) tissues and miR-195 was downregulated in ESCC compared with normal esophageal tissues. Moreover, Cdc42 was confirmed as target gene of miR-195. Ectopic expression of miR-195 in ESCC cells significantly downregulated Cdc42 by directly binding its 3′ untranslated regions, and induced G1 cell cycle arrest, leading to a significant decrease in cell growth, migration, and invasion in vitro. Therefore, our findings demonstrated that miR-195 may act as a tumor suppressor in ESCC by targeting Cdc42.     

Analyses in human urothelial cells identify methylation of miR-152, miR-200b and miR-10a genes as candidate bladder cancer biomarkers

Urinary miRNAs are discussed as potential biomarkers for bladder cancer. The majority of miRNAs, however, are downregulated, making it difficult to utilize reduced miRNA signals as reliable diagnostic tools. Because the downregulation of miRNAs is frequently associated with hypermethylation of the respective regulative sequences, we studied whether DNA hypermethylation might serve as an improved diagnostic tool compared to measuring downregulated miRNAs. miRNA expression arrays and individual qPCR were used to identify and confirm miRNAs that were downregulated in malignant urothelial cells (RT4, 5637 and J82) when compared to primary, non-malignant urothelial cells (HUEPC). DNA methylation was determined by customized PCR-arrays subsequent to methylation-sensitive DNA-restriction and by mass spectrometry. miRNA expression and DNA methylation were determined in untreated cells and in cultures treated with the demethylating agent 5-Aza-2′-deoxycytidine. miR-200b, miR-152 and miR-10a displayed differential expression and methylation among untreated cancer cell lines. In addition, reduced miRNA expression of miR-200b, miR-152, and miR-10a was associated with increased DNA methylation in malignant cells versus HUEPC. Finally, the demethylation approach revealed a causal relationship between both parameters for miR-152 in 5637 and also suggests a causal connection of both parameters for miR-200b in J82 and miR-10a in 5637. In conclusion, our studies in multiple bladder cancer cell lines and primary non-malignant urothelial cells suggest that hypermethylation of miR-152, miR-10a and miR-200b regulative DNA sequences might serve as epigenetic bladder cancer biomarkers.     

Comparisons of microRNA Patterns in Plasma before and after Tumor Removal Reveal New Biomarkers of Lung Squamous Cell Carcinoma

Lung cancer is the major human malignancy, accounting for 30% of all cancer-related deaths worldwide. Poor survival of lung cancer patients, together with late diagnosis and resistance to classic chemotherapy, highlights the need for identification of new biomarkers for early detection. Among different cancer biomarkers, small non-coding RNAs called microRNAs (miRNAs) are considered the most promising, owing to their remarkable stability, their cancer-type specificity, and their presence in body fluids. However, results of multiple previous attempts to identify circulating miRNAs specific for lung cancer are inconsistent, likely due to two main reasons: prominent variability in blood miRNA content among individuals and difficulties in distinguishing tumor-relevant miRNAs in the blood from their non-tumor counterparts. To overcome these impediments, we compared circulating miRNA profiles in patients with lung squamous cell carcinoma (SCC) before and after tumor removal, assuming that the levels of all tumor-relevant miRNAs would drop after the surgery. Our results revealed a specific panel of the miRNAs (miR-205, -19a, -19b, -30b, and -20a) whose levels decreased strikingly in the blood of patients after lung SCC surgery. Interestingly, miRNA profiling of plasma fractions of lung SCC patients revealed high levels of these miRNA species in tumor-specific exosomes; additionally, some of these miRNAs were also found to be selectively secreted to the medium by cultivated lung cancer cells. These results strengthen the notion that tumor cells secrete miRNA-containing exosomes into circulation, and that miRNA profiling of the exosomal plasma fraction may reveal powerful cancer biomarkers.     

The diagnostic efficacy of circulating miRNAs in monitoring the early development of colitis-induced colorectal cancer

Early detection of colorectal cancer and monitoring the progress in colon carcinogenesis stages is essential to reduce mortality. Therefore, there is continuous search for noninvasive biomarkers with high stability and good sensitivity and specificity. miRNAs have attracted attention as promising biomarkers as they are stably expressed in circulation. The aim of our study is to evaluate the aberrant expression of circulating miRNAs during the stepwise progress of colitis-associated colon cancer. This was accomplished through assessing the expression levels of five miRNAs (miR-141, miR-15b, miR-17-3p, miR-21, and miR-29a) in serum and their corresponding tissue samples through the different cycles of colorectal carcinogenesis cascade using the azoxymethane/dextran sulfate sodium murine model. We also compared the diagnostic performance of these selected miRNAs with the conventional tumor biomarkers CEA and CA 19-9. The results of our study revealed that the expression levels of those miRNAs were dynamically changing in accordance with the tumor development state. Moreover, their aberrant expression in serum was statistically correlated with that in tissue. Our data also revealed that serum miR-15b, miR-21, and miR-29a showed the best performance in terms of diagnostic power. Our findings highlight the efficiency of these circulating miRNAs not only for early diagnostics purposes, but also for monitoring progress in the colorectal carcinogenesis process, and therefore encouraging integrating these noninvasive biomarkers into the clinical diagnostic settings beside the traditional diagnostic markers for accurate screening of the early progress of colon carcinogenesis.     

MicroRNA expression profile in serum reveals novel diagnostic biomarkers for endometrial cancer

Purpose: Circulating microRNAs (miRNAs) prove to be promising diagnostic biomarkers for various cancers, including endometrial cancer (EC). The present study aims to identify serum microRNAs that can serve as potential biomarkers for EC diagnosis.Patients and methods: A total of 92 EC and 102 normal control (NC) serum samples were analyzed using quantitative real-time polymerase chain reaction (qRT-PCR) in this four-phase experiment. The logistic regression method was used to construct a diagnostic model based on the differentially expressed miRNAs in serum. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value. To further validate the diagnostic capacity of the identified signature, the 6-miRNA marker was compared with previously reported biomarkers and verified in three public datasets. In addition, the expression characteristics of the identified miRNAs were further explored in tissue and serum exosomes samples.Results: Six miRNAs (miR-143-3p, miR-195-5p, miR-20b-5p, miR-204-5p, miR-423-3p, and miR-484) were significantly overexpressed in the serum of EC compared with NCs. Areas under the ROC of the 6-miRNA signatures were 0.748, 0.833, and 0.967 for the training, testing, and the external validation phases, respectively. The identified signature has a very stable diagnostic performance in the large cohorts of three public datasets. Compared with previously identified miRNA biomarkers, the 6-miRNA signature in the present study has superior performance in diagnosing EC. Moreover, the expression of miR-143-3p and miR-195-5p in tissues and the expression of miR-20b-5p in serum exosomes were consistent with those in serum.Conclusions: We established a 6-miRNA signature in serum and they could function as potential non-invasive biomarker for EC diagnosis.