• CircRNA
• Drug resistance
• Immune evasion
• LncRNA
• MicroRNA
• Non-coding RNA

• Cell Proliferation/genetics
• Colorectal Neoplasms/pathology
• Down-Regulation
• Gene Expression Regulation, Neoplastic
• Hepatocyte Nuclear Factor 4/genetics
• Hepatocyte Nuclear Factor 4/metabolism
• Humans
• MicroRNAs/metabolism
• Phosphatidylinositol 3-Kinases/genetics
• Phosphatidylinositol 3-Kinases/metabolism
• Proto-Oncogene Proteins c-akt/genetics
• Proto-Oncogene Proteins c-akt/metabolism

Previous work has demonstrated that the expression of microRNA-21 (miR-21) is implicated in cervical cancer (CC). However, little is known regarding its associations with clinical parameters. We first conducted a meta-analysis using data from Gene Expression Omnibus (GEO) microarrays and The Cancer Genome Atlas (TCGA). Then, enrichment analysis and hub gene screening were performed by bioinformatic methods. Finally, the role of the screened target genes in CC was explored. According to the meta-analysis, the expression of miR-21 in cancer tissues was higher than in adjacent nontumor tissues (P < 0.05). In addition, 46 genes were predicted as potential targets of miR-21. After enrichment analyses, it was detected that these genes were enriched in various cancer pathways, including the phosphatidylinositol signaling system and mammalian target of rapamycin (mTOR) signaling pathway. In this study, bioinformatic tools and meta-analysis validated that miR-21 may function as a highly sensitive and specific marker for the diagnosis of CC, which may provide a novel approach to the diagnosis and treatment of CC.

• Computational Biology/methods
• Female
• Gene Expression Profiling/methods
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs/genetics
• Uterine Cervical Neoplasms/genetics

• Key Research and Development Program of Hubei Province
• Natural Science Foundation of China

• analysis
• biomarkers
• diagnosis
• hepatocellular carcinoma
• miR-21

• RT-qPCR.
• biomarker
• clinicopathological features
• diagnosis
• endometrial cancer
• microRNAs

观察microRNA-21（miR-21）敲除对耐伊马替尼的人慢性髓性白血病细胞株K562/G01细胞在增殖、药物敏感性等方面的影响，初步探讨miR-21影响K562/G01细胞伊马替尼敏感性的可能机制。

运用CRISPR/Cas9技术敲除K562/G01细胞的miR-21，经PCR筛选、Sanger测序鉴定和实时定量PCR检测获得miR-21敲除的单细胞克隆。扩增培养后，采用MTT法、细胞克隆形成实验检测miR-21敲除对K562/G01细胞增殖的影响。使用伊马替尼处理细胞后，用MTT法和Annexin Ⅴ-APC/7-AAD双染流式细胞检测法观察敲除miR-21后K562/G01细胞对伊马替尼的敏感性的变化。Western blot法检测miR-21敲除前后K562/G01细胞PTEN、AKT、p-AKT、PI3K、p-PI3K、P210^BCR-ABL、p-P210^BCR-ABL蛋白表达量的变化。

成功构建了3个miR-21敲除的K562/G01单细胞克隆，CRISPR/Cas9介导的突变效率为7.12％～8.11％。miR-21敲除使K562/G01细胞的增殖受抑，野生型和1#、2#、6#单细胞克隆的克隆形成率依次为（57.67±8.25）％、（26.94±5.36）％、（7.17±2.11）％、（31.50±3.65）％，差异有统计学意义（P<0.05）。miR-21敲除使K562/G01细胞对伊马替尼的敏感性增加，野生型和1#、2#、6#单细胞克隆对伊马替尼的IC₅₀值分别为（21.92±1.36）µmol/ml、（3.98±0.39）µmol/ml、（5.38±1.01）µmol/ml、（9.24±1.36）µmol/ml，差异有统计学意义（P<0.05）。miR-21敲除后，其靶基因PTEN的蛋白表达水平未见明显变化，但PI3K、AKT信号分子的活化受到抑制，并且P210^BCR-ABL、p-P210^BCR-ABL蛋白表达也下调。

miR-21敲除抑制K562/G01细胞增殖，提高其对伊马替尼的敏感性，这可能是通过抑制PI3K/AKT信号通路和BCR-ABL表达实现的。

• CRISPR/Cas9
• Chronic myeloid leukemia
• Knockout
• imatinib
• miR-21

Primary prevention of premature death is a public health concern worldwide. Circulating microRNAs (miRNAs) have been described as potential diagnostic biomarkers for diseases as cancer and cardiovascular disease (CVD). This case-cohort study aimed to investigate the potential relationship between circulating miRNAs and the risk of premature death. A total of 39,242 subjects provided baseline serum samples in 1988–1990. Of these, 345 subjects who died of intrinsic disease (< 65 years old) and for which measurable samples were available were included in this study. We randomly selected a sub-cohort of 879 subjects. Circulatring miR-21, miR-29a, and miR-126 were determined using qRT-PCR. Conditional logistic regression models were used to analyse the data with respect to stratified miRNA levels. Multivariable logistic regression revealed that subjects with high circulating miR-21 and miR-29a individual levels had a significantly higher risk of total death, cancer death, and CVD death than those with medium miR-21 and miR-29a individual levels. Conversely, subjects with low circulating miR-126 levels had a significantly higher risk of total death than those with medium levels. This suggests that circulating miRNAs are associated with the risk of premature death from cancer and CVD, identifying them as potential biomarkers for early detection of high-risk individuals.

• Adenoma
• colorectal cancer
• diagnostic biomarker
• epigenomics
• genomics
• metabolomics
• proteomics
• serrated lesion
• transcriptomics
• transference

• biomarkers
• chemoradiotherapy
• miR-21
• rectal cancer
• therapy response
• tumor regression grade

• SAICTPAC/0019/2015 FCT - Fundação para a Ciência e a Tecnologia
• LISBOA-01-0145-FEDER-016405 European Structural & Investment Funds through the COMPETE Programme - Programa Operacional Regional de Lisboa

• Exosomal RNA
• cancer monitoring
• early detection
• exoRNA
• noninvasive screening

• Base Sequence
• Biomarkers, Tumor/blood
• Biomarkers, Tumor/isolation & purification
• Carcinoma/blood
• Carcinoma/diagnosis
• Carcinoma/pathology
• Carcinoma/therapy
• Cell-Free Nucleic Acids/blood
• Cell-Free Nucleic Acids/isolation & purification
• Drug Resistance, Neoplasm
• Early Detection of Cancer/methods
• Exosomes/chemistry
• Female
• Flow Cytometry/methods
• Humans
• Male
• MicroRNAs/blood
• MicroRNAs/isolation & purification
• Microarray Analysis
• Nanotechnology/instrumentation
• Nanotechnology/methods
• Neoplasm Staging/methods
• Neoplasms/blood
• Neoplasms/genetics
• Prognosis
• RNA, Neoplasm/blood
• RNA, Neoplasm/isolation & purification
• Real-Time Polymerase Chain Reaction
• Sensitivity and Specificity
• Ultracentrifugation/methods

• Exosomes
• Intercellular communication
• MicroRNAs

This systematic analysis aimed to investigate the value of microRNA-21 (miR-21) in colorectal cancer for multiple purposes, including diagnosis and prognosis, as well as its predictive power in combination biomarkers. Fifty-seven eligible studies were included in our meta-analysis, including 25 studies for diagnostic meta-analysis and 32 for prognostic meta-analysis. For the diagnostic meta-analysis of miR-21 alone, the overall pooled results for sensitivity, specificity, and area under the curve (AUC) were 0.64 (95% CI: 0.53-0.74), 0.85 (0.79-0.90), and 0.85 (0.81-0.87), respectively. Circulating samples presented corresponding values of 0.72 (0.63-0.79), 0.84 (0.78-0.89), and 0.86 (0.83-0.89), respectively. For the diagnostic meta-analysis of miR-21-related combination biomarkers, the above three parameters were 0.79 (0.69-0.86), 0.79 (0.68-0.87), and 0.86 (0.83-0.89), respectively. Notably, subgroup analysis suggested that miRNA combination markers in circulation exhibited high predictive power, with sensitivity of 0.85 (0.70-0.93), specificity of 0.86 (0.77-0.92), and AUC of 0.92 (0.89-0.94). For the prognostic meta-analysis, patients with higher expression of miR-21 had significant shorter disease-free survival [DFS; pooled hazard ratio (HR): 1.60; 95% CI: 1.20-2.15] and overall survival (OS; 1.54; 1.27-1.86). The combined HR in tissues for DFS and OS were 1.76 (1.31-2.36) and 1.58 (1.30-1.93), respectively. Our comprehensive systematic review revealed that circulating miR-21 may be suitable as a diagnostic biomarker, while tissue miR-21 could be a prognostic marker for colorectal cancer. In addition, miRNA combination biomarkers may provide a new approach for clinical application.

• colorectal cancer
• diagnosis
• meta-analysis
• miR-21
• prognosis

Colorectal cancer (CRC) is a major cause of deaths worldwide but has a good prognosis if detected early. The need for efficient, preferable non‐ or minimally invasive, inexpensive screening tools is therefore critical. We analyzed 12 miRNAs in pre‐ and postdiagnostic plasma samples to evaluate their potential as CRC screening markers. We used a unique study design with two overlapping cohorts, allowing analysis of pre‐ and postdiagnostic samples from 58 patients with CRC and matched healthy controls. Plasma concentrations of miR‐15b, ‐16, ‐18a, ‐19a, 21, ‐22, ‐25, ‐26a, ‐29c, ‐142‐5p, ‐150, and ‐192 were measured by semi‐quantitative real‐time PCR. Concentrations of miR‐18a, ‐21, ‐22, and ‐25 in plasma from patients with CRC were significantly altered compared to healthy controls. Combined as a multimarker panel, they detected CRC with an AUC of 0.93. Furthermore, levels of these three miRNAs also showed different levels in the prediagnostic case samples close to diagnosis. Only miR‐21‐levels were elevated several years before diagnosis. Plasma levels of miR‐18a, ‐21, ‐22, and ‐25 show promise as screening biomarkers for CRC. However, based on our unique analysis of prediagnostic and postdiagnostic samples from the same patients, we conclude that circulating miRNAs elevated at diagnosis may not automatically be suitable for CRC screening, if the increase occurs too close to clinical diagnosis.

• Colorectal cancer
• early detection
• plasma miRNA

MiR-21 has been identified as one of the most common proto-oncogenes. It is hypothesized that up-regulated miR-21 could be served as a potential biomarker for human cancer diagnosis. However, inconsistencies or discrepancies about diagnostic accuracy of circulating miR-21 still remain. In this sense, miR-21′s diagnostic value needs to be fully validated. In this study, we performed an update meta-analysis to estimate the diagnostic value of circulating miR-21 in various human cancers. Additionally, we conducted a validation test on 50 endometrial cancer patients, 50 benign lesion patients and 50 healthy controls. A systematical literature search for relevant articles was performed in Pubmed, Embase and Cochrane Library. A total of 48 studies from 39 articles, involving 3,568 cancer patients and 2,248 controls, were included in this meta-analysis. The overall sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the curve (AUC) were 0.76 (0.71-0.80), 0.82 (0.79-0.85), 4.3 (3.6-5.1), 0.29 (0.24-0.35), 15 (11-20) and 0.86 (0.83-0.89), respectively. In the validation test, the expression levels of serum miR-21 were significantly higher in benign lesion patients (p = 0.003) and endometrial cancer patients (p = 0.000) compared with that of healthy controls. Endometrial cancer patients showed higher miR-21 expression levels (p = 0.000) compared with benign lesion patients. In conclusion, the meta-analysis shows that circulating miR-21 has excellent performance on the diagnosis for various cancers and the validation test demonstrates that serum miR-21 could be served as a novel biomarker for endometrial carcinoma.

• cancers
• diagnosis
• endometrial carcinoma
• meta-analysis
• miR-21

• Colorectal cancer
• Diagnosis
• Isothermal
• Near-infrared (NIR)
• Optical imaging
• Ytterbium
• miRNA

• colorectal cancer
• diagnosis
• microRNA
• therapy

MicroRNAs (miRNAs) are small RNAs regulate gene expression by inhibiting the turnover of their target mRNAs. In the last years, it became apparent that miRNAs are released into the circulation and circulating miRNAs emerged as a new class of biomarkers for various diseases. In this review we summarize available data on the role of circulating miRNAs in the context of acute and chronic liver diseases including hepatocellular and cholangiocellular carcinoma. Data from animal models are compared to human data and current challenges in the field of miRNAs research are discussed.

• Liver disease
• Acute liver failure
• MicroRNA
• Liver fibrosis
• Hepatocellular carcinoma
• Autoimmune hepatitis
• Cholangiocarcinoma

• CRC
• EMT
• NR2F2
• Smad7
• miR-21

• Biomarkers
• Cancer
• Cardiovascular disease
• Diabetes
• MiRNAs
• Toxicology

MicroRNAs (miRNAs) are a class of endogenous, evolutionarily conserved small non-coding RNAs, which play a vital role in tumour formation, development, metastasis and recurrence by inducing DNA methylation, changing tumor microenvironment and regulating signal pathways such as Wnt/β-catenin, phosphoinositide3-kinase (PI3K), K-RAS, epithelial mesenchymal transitions (EMT) and so on. Recent studies have found that the expression of many miRNAs is dyregulated in colorectal cancer, and they participate in and control the formation and development of colorectal cancer. Thus, understanding the roles and mechanisms of action of miRNAs in colorectal cancer can provide a new avenue for its early diagnosis, clinical staging, treatment and prognosis evaluation.

• MicroRNAs
• Colorectal cancer
• Signal pathway
• Early diagnosis
• Prognosis evaluation

MiR-381 has been reported to be dysregulated in several human cancers. However, the function and mechanism of miR-381 in colorectal cancer (CRC) remains unclear. In the present study, the miR-381 expression was assessed in a cohort of 113 CRC specimens using real-time quantitative polymerase chain reaction (RTq-PCR), which demonstrated that miR-381 was significantly downregulated in CRC and correlated with distant metastasis and tumor, node, and metastasis (TNM) stage. Functional study revealed that restoration of miR-381 significantly inhibited the invasion, migration, and epithelial–mesenchymal transition (EMT) of CRC cells. Luciferase reporter assay validated that Twist1, an important EMT inducer, was a direct target of miR-381, and rescued Twist1 attenuated the function of miR-381 in CRC cells. Correlation analysis also revealed an inverse correlation between miR-381 and Twist1 expression levels in CRC specimens. Taken together, our results highlight the significance of miR-381/Twist1 interaction in the development and progression of CRC, and suggest that restoration of miR-381 may be a potential therapeutic strategy for the patients with CRC.

• EMT
• Twist1
• colorectal cancer
• epithelial–mesenchymal transition
• miR-381
• twist family bHLH transcription factor 1

Obesity and metabolic syndrome are growing epidemics worldwide and greatly responsible for many liver diseases, including nonalcoholic fatty liver disease (NAFLD). NAFLD often progresses to cirrhosis, end-stage liver failure and hepatocellular carcinoma (HCC), the most common primary liver cancer and one of the leading causes for cancer-related deaths globally. Currently available tools for the diagnosis of NAFLD staging and progression towards HCC are largely invasive and of limited accuracy. In light of the need for more specific and sensitive noninvasive molecular markers, several studies have assessed the potential of circulating microRNAs (miRNAs) as biomarkers of liver injury and hepatocarcinogenesis. Indeed, extracellular miRNAs are very stable in the blood, can be easily quantitated and are differentially expressed in response to different pathophysiological conditions. Although standardization procedures and larger, independent studies are still necessary, miRNAs constitute promising, clinically-useful biomarkers for the NAFLD-HCC spectrum.

• biomarker
• hepatocellular carcinoma
• liver
• microRNA
• nonalcoholic fatty liver disease
• plasma
• serum

• biomarker
• colorectal neoplasm
• metastasis
• miRNA
• target gene

• Animals
• Biomarkers, Tumor/genetics
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/pathology
• Disease Progression
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs/genetics

For two decades Vogelstein’s model has been the paradigm for describing the sequence of molecular changes within protein-coding genes that would lead to overt colorectal cancer (CRC). This model is now too simplistic in the light of recent studies, which have shown that our genome is pervasively transcribed in RNAs other than mRNAs, denominated non-coding RNAs (ncRNAs). The discovery that mutations in genes encoding these RNAs [i.e., microRNAs (miRNAs), long non-coding RNAs, and circular RNAs] are causally involved in cancer phenotypes has profoundly modified our vision of tumour molecular genetics and pathobiology. By exploiting a wide range of different mechanisms, ncRNAs control fundamental cellular processes, such as proliferation, differentiation, migration, angiogenesis and apoptosis: these data have also confirmed their role as oncogenes or tumor suppressors in cancer development and progression. The existence of a sophisticated RNA-based regulatory system, which dictates the correct functioning of protein-coding networks, has relevant biological and biomedical consequences. Different miRNAs involved in neoplastic and degenerative diseases exhibit potential predictive and prognostic properties. Furthermore, the key roles of ncRNAs make them very attractive targets for innovative therapeutic approaches. Several recent reports have shown that ncRNAs can be secreted by cells into the extracellular environment (i.e., blood and other body fluids): this suggests the existence of extracellular signalling mechanisms, which may be exploited by cells in physiology and pathology. In this review, we will summarize the most relevant issues on the involvement of cellular and extracellular ncRNAs in disease. We will then specifically describe their involvement in CRC pathobiology and their translational applications to CRC diagnosis, prognosis and therapy.

• Colorectal cancer
• MicroRNA
• Long non-coding RNAs
• Circular RNAs
• Diagnosis
• Prognosis
• Therapy

• Animals
• Biomarkers, Tumor/genetics
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/pathology
• Gene Expression Regulation, Neoplastic
• Gene Regulatory Networks
• Genetic Predisposition to Disease
• Genome, Human
• Humans
• Molecular Diagnostic Techniques
• Phenotype
• Predictive Value of Tests
• Prognosis
• RNA, Neoplasm/genetics
• RNA, Untranslated/genetics
• Risk Factors

• Biomarkers, Tumor/metabolism
• Chemoradiotherapy
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Logistic Models
• Male
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Middle Aged
• Multivariate Analysis
• Neoplasm Staging
• ROC Curve
• Rectal Neoplasms/genetics
• Rectal Neoplasms/pathology
• Rectal Neoplasms/therapy
• Treatment Outcome

• Biomarkers, Tumor/genetics
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/genetics
• Humans
• Liver Neoplasms/diagnosis
• Liver Neoplasms/genetics
• MicroRNAs/genetics