• Alzheimer’s disease
• Apoptosis
• Bioinformatics
• Cuproptosis

• Alzheimer Disease/genetics
• Humans
• Computational Biology/methods
• Protein Interaction Maps/genetics
• Gene Regulatory Networks
• Gene Expression Profiling/methods
• Apoptosis/genetics
• Databases, Genetic

• AFF3
• Mendelian randomization
• Renal cancer
• SMR
• eQTL

• Humans
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Kidney Neoplasms/genetics
• Mendelian Randomization Analysis
• Polymorphism, Single Nucleotide
• Quantitative Trait Loci

• SEL1L3
• atherosclerosis
• bioinformatics
• potential biomarker
• renal cancer

• Humans
• Carcinoma, Renal Cell/genetics
• Carcinoma, Renal Cell/pathology
• Gene Expression Profiling/methods
• Gene Regulatory Networks
• Biomarkers, Tumor/genetics
• Kidney Neoplasms/genetics
• Transcription Factors/genetics
• Computational Biology/methods

Gastric cancer(GC)is one of the deadliest digestive tract tumors worldwide，existing studies suggest that dysregulated expression of microRNAs (miRNAs) plays an important role in the pathogenesis and progression of GC. This study aimed to investigate the expression, biological function, and downstream mechanism of miR-34c-5p in GC, provide new targets for gastric cancer diagnosis and treatment.

The expression of miR-34c-5p in GC tissues and cell lines was examined by RT-qPCR. Cell wound healing, transwell and cell cloning assays were used to detect the effect of miR-34c-5p on the migration and invasion abilities, respectively, of GC cells. Western blot was performed to detect the expression of related proteins. Bioinformatics analysis was used to predict the binding of MAP2K1 to miR-34c-5p and the targeting relationship was confirmed by dual luciferase reporter assay.

The expression level of miR-34c-5p was significantly decreased in GC tissues and cell lines. miR-34c-5p overexpression inhibited migration, invasion, and colony formation of gastric cancer cells, the related protein E-cadherin expression was significantly increased and N-cadherin, vimentin, and PCNA expression were significantly decreased, while miR-34c-5p knockdown exerted the opposite effects. In addition, the targeting relationship between miR-34c-5p and MAP2K1 was predicted and confirmed, and further confirmed by rescue experiments that MAP2K1 alleviated the inhibitory effect of miR-34c-5p in GC.

MiR-34c-5p is lowly expressed in GC, and it can target MAP2K1 to exert inhibitory effects on GC proliferation, invasion, and migration. These findings provide a promising biomarker and a potential therapeutic target for gastric cancer.

• IR score
• chemo drugs
• clear cell renal cell carcinoma
• immune checkpoint blockade
• immunotherapy
• molecular subtype
• tumor microenvironment

miRNAs can act as oncogenes or tumor suppressors and participate in the development and progression of tumors, thus affecting the prognosis and survival of cancer patients. In this paper, we mainly studied the role of miR-1826 in prostate cancer.

The expression of miR-1826 was studied by quantitative real-time PCR (qRT-PCR). Kaplan–Meier curves were used to analyze the relationship between the expression of miR-1826 and the survival rate of PC patients. Cox regression analysis was used to study the risk factors affecting the prognosis of PC patients. PC cells were transfected with miR-1826 mimic, mimic negative control (mimic NC), miR-1826 inhibitor, or inhibitor NC. The effect of miR-1826 on the proliferation of PC cells was studied by the CCK-8 method and colony formation assay. Transwell assays were used to detect the effect of miR-1826 on the migratory and invasive abilities of tumor cells.

The expression of miR-1826 in PC tissues was lower than that in adjacent normal tissues, and that the expression levels of miR-1826 in four PC cell lines were all lower than normal human prostate epithelial cell lines. Patients with low expression of miR-1826 had shorter overall survival compared with those with high expression. The downregulation of miR-1826 promoted PC cell proliferation, migration, and invasion.

In summary, the low expression of miR-1826 may promote the progression of PC, and the low expression of miR-1826 is also associated with a poor prognosis in PC patients.

• miR-1826
• prognostic value
• progression
• prostate cancer
• treatment

Background: Current staging systems are inadequate for evaluating the prognosis of patients with locally advanced gastric cancer (LAGC, stages II–III). Therefore, we developed a serum microRNA (miRNA) signature to facilitate individualized management of these patients.

Methods: Using microarray analysis, we analyzed 12 serum specimens based on different prognoses (good survival group, n = 7; poor survival group, n = 5). We identified and confirmed differential expression of these miRNAs using quantitative reverse transcription PCR (qRT-PCR) of serum from 51 patients with LAGC. A three miRNA-based classifier was established as a training set by Cox proportional hazard regression and risk-score analysis. We validated the prognostic accuracy of this model in an internal validation cohort (Sun Yat-Sen University Cancer Center, SYSUCC validation cohort, n = 50) and an external independent cohort (Beijing Cancer Hospital, BJCH cohort, n = 67).

Results: Three miRNAs were found to be associated with survival of LAGC (P < 0.001 for miR-132, P = 0.011 for miR-548a-3p, and P < 0.001 for miR-1826). A three-miRNA signature was developed for the training set, and a significant difference was found between the survival of low- and high-risk score patients (P < 0.01). The combination of the miRNA signature and tumor–node–metastasis (TNM) stage exhibited superior discrimination. Consistent results were obtained by further validation of the internal set and the BJCH set, which confirmed the predictive value of the model.

Conclusions: We built an easy-to-use prognostic signature using three serum miRNAs as markers. Our miRNA signature may improve postoperative risk stratification and serve as a complement to the TNM staging system.

• advanced gastric cancer
• microRNA
• prognosis
• serum
• survival

• intranasal administration
• major depression disorder
• miR-214
• β-catenin

Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy worldwide. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been identified as effective markers for the detection of multiple cancers. This study aimed to illuminate the mechanism of prostate androgen regulated transcript 1 (PART1) in HCC.

The levels of PART1, miR-149-5p and mitogen-activated protein kinase 1 (MAP2K1) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) assay, and cell migration and invasion were evaluated by transwell assay. Dual-luciferase reporter assay was carried out to examine the relationship among PART1, miR-149-5p and MAP2K1. Western blot assay was conducted to measure the protein expression of MAP2K1.

PART1 and MAP2K1 expression were greatly increased and miR-149-5p level was decreased in HCC tissues. Functional analysis revealed that the si-PART1 inhibited proliferation, migration and invasion of HCC cells. PART1 directly bound to miR-149-5p and miR-149-5p level was down-regulated by PART1. Moreover, restoration experiment demonstrated that the effect of PART1 knockdown on HCC cell progression could be partially rescued by miR-149-5p depletion. MiR-149-5p was predicted to target MAP2K1 and MAP2K1 expression was negatively modulated by miR-149-5p. Also, MAP2K1 rescued the inhibitory effects of miR-149-5p overexpression on proliferation, migration and invasion in HCC cells. Besides, the inhibition of miR-149-5p weakened the impact on MAP2K1 expression mediated by PART1 repression.

PART1 promoted proliferation, migration and invasion of HCC cells by regulating miR-149-5p/MAP2K1 axis.

• MAP2K1
• PART1
• hepatocellular carcinoma
• miR-149-5p

• cancer
• centrality
• driver gene
• protein–protein network
• random walk

Osteosarcoma (OS) is the most frequent bone tumor with high metastasis. This study is aimed at assessing the expression and prognostic significance of microRNA-1826 (miR-1826) in OS patients, as well as its biological function in tumor progression.

Quantitative Real-Time PCR was employed to measure the expression of miR-1826 in OS tissues and cell lines. Kaplan-Meier survival analysis and Cox regression model were used to evaluate the prognostic value of miR-1826. CCK-8 and Transwell assay were conducted to investigate the effect of miR-1826 on OS cell proliferation, migration, and invasion.

miR-1826 expression was downregulated in OS tissues and cell lines and associated with OS patients' clinical stage and distant metastasis. Low levels of miR-1826 were related with shorter survival time and determined as an independent prognostic indicator for the overall survival of OS patients. The overexpression of miR-1826 in OS cells led to inhibited cell proliferation, migration, and invasion.

The decreased expression of miR-1826 predicts a poor prognosis in OS patients, and its overexpression inhibits OS cell proliferation, migration, and invasion. This newly identified miR-1826 provides a novel sight into the pathogenesis of OS and offers a candidate prognostic biomarker and therapeutic target for OS treatment.

δ‐Catenin is a unique member of the catenin family and is proved to be overexpressed in diverse human cancer types. However, the clinical significance and underling mechanism of δ‐catenin expression in renal cell carcinoma (RCC) remain elusive. Herein, we detected the protein expression of δ‐catenin in 28 clinical specimens of paired renal cancer tissues and normal renal tissues by Western blot analysis. δ‐Catenin expression in 58 cases of renal cell carcinoma was also examined by immunohistochemistry, and its association with clinicopathological factors was analyzed by statistical analysis. In vitro and in vivo assays were employed to further explore the biological role of δ‐catenin in RCC. The results showed that δ‐catenin was highly expressed in both clinical samples and cell lines of RCC. RCC patients with higher δ‐catenin expression had a more advanced pTNM stage and tumor stage as well as lymph nodes metastasis than those with lower expression. By regulating the nuclear translocation of β‐catenin and β‐catenin‐mediated oncogenic signals, δ‐catenin promoted proliferation and inhibited apoptosis in RCC. In vivo assay indicated δ‐catenin facilitated tumor growth in ACHN cell xenograft mouse model. Taken together, our study suggests that δ‐catenin might be considered as a novel prognostic indicator and actionable target for gene therapy in renal cell carcinoma.

• apoptosis
• proliferation
• renal cell carcinoma
• β-catenin
• δ-catenin

• a disintegrin and metalloproteinase 9
• microRNA-30a
• progression
• renal cell carcinoma

The Wnt/β-catenin signaling is crucial for the proliferation and migration of breast cancer cells. However, the expression of microRNA-224 (miR-224) in the different types of breast cancers and its role in the Wnt/β-catenin signaling and the proliferation and migration of breast cancer cells are poorly understood. In this study, the levels of miR-224 in different types of breast cancer tissues and cell lines were examined by quantitative RT-PCR and the potential targets of miR-224 in the Wnt/β-catenin signaling were investigated. The effects of altered miR-224 expression on the frequency of CD44⁺CD24⁻ cancer stem-like cells (CSC), proliferation and migration of MCF-7 and MDA-MB-231 cells were examined by flow cytometry, MTT and transwell migration. We found that the levels of miR-224 expression in different types of breast cancer tissues and cell lines were associated inversely with aggressiveness of breast cancers. Enhanced miR-224 expression significantly reduced the fizzled 5-regulated luciferase activity in 293T cells, fizzled 5 expression in MCF-7 and MDA-MB-231 cells, the β-dependent luciferase activity in MCF-7 cells, and the nuclear translocation of β-catenin in MDA-MB-231 cells. miR-224 inhibition significantly increased the percentages of CSC in MCF-7 cells and enhanced proliferation and migration of MCF-7 cells. Enhanced miR-224 expression inhibited proliferation and migration of MDA-MB-231 cells, and the growth of implanted breast cancers in vivo. Induction of frizzled 5 over-expression mitigated the miR-224-mediated inhibition of breast cancer cell proliferation. Collectively, these data indicated that miR-224 down-regulated the Wnt/β-catenin signaling possibly by binding to frizzled 5 and inhibited proliferation and migration of breast cancer cells.

• MiR-224
• Wnt/β-catenin signaling
• breast cancer cells
• migration
• proliferation

Mounting evidence has indicated microRNA (miR) dysregulation and the Wnt/β-catenin signaling pathway jointly drive carcinogenesis, cancer metastasis, and drug-resistance. The current review will focus on the role of the crosstalk between miRs and the Wnt/β-catenin signaling pathway in cancer development. MiRs were found to activate or inhibit the canonical Wnt pathway at various steps. On the other hand, Wnt activation increases expression of miR by directly binding to its promoter and activating transcription. Moreover, there are mutual feedback loops between some miRs and the Wnt/β-catenin signaling pathway. Clinical trials of miR-based therapeutic agents are investigated for solid and hematological tumors, however, challenges concerning low bioavailability and possible side effects must be overcome before the final clinical application. This review will describe current understanding of miR crosstalk with the Wnt/β-catenin signaling cascade. Better understanding of the regulatory network will provide insight into miR-based therapeutic development.

• Wnt/β-catenin signaling pathway
• cancer
• microRNA

• Cancer hallmarks
• Coding gene targets
• Immunotherapy
• Invasion
• MicroRNAs
• Proliferation
• Targeted therapy

• DNA-methylation
• SF2
• miR-766-3p
• proliferation
• renal cell carcinoma

• Hepatocellular carcinoma
• MiR-106b
• ROC curve
• Random sampling survey

• Aged
• Alcohol Drinking
• Area Under Curve
• Biomarkers, Tumor/blood
• Biopsy
• Carcinoma, Hepatocellular/blood
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Liver Neoplasms/blood
• Male
• MicroRNAs/blood
• Middle Aged
• Obesity/blood
• ROC Curve
• Ultrasonography

MicroRNAs (miRs) have emerged as key epigenetic regulators involved in cancer progression. miR-320a has been demonstrated to be a novel tumor suppressive microRNA in several types of cancers. In the present study, the role of miR-320a in human hepatocellular carcinoma (HCC) was investigated. The expression levels of miR-320a and messenger RNA were determined by reverse transcription-quantitative polymerase chain reaction, while cell cycle and cell apoptosis were analyzed by flow cytometry. The cell proliferative ability was determined by Cell Counting Kit-8 assay and colony formation assay. The downstream target of miR-320a was confirmed by luciferase reporter assay, while the protein levels were measured by western blotting. The results revealed that miR-320a was inversely associated with HCC proliferation in HCC cell lines. Functional studies demonstrated that miR-320a significantly decreased the capability of cell proliferation and induced G₀/G₁ growth arrest in vitro. In addition, β-catenin was identified as one of the direct targets of miR-320a, downregulating the expression level of β-catenin, c-myc, cyclin D1 and dickkopf-1. In conclusion, miR-320a may act as a tumor-suppressive microRNA through targeting β-catenin in HCC.

• hepatocellular carcinoma
• microRNA-320a
• proliferation
• β-catenin

Cellular junctions play a critical role in structural connection and signal communication between cells in various tissues. Although there are structural and functional varieties, cellular junctions include tight junctions, adherens junctions, focal adhesion junctions, and tissue specific junctions such as PECAM-1 junctions in endothelial cells (EC), desmosomes in epithelial cells, and hemidesmosomes in EC. Cellular junction dysfunction and deterioration are indicative of clinical diseases. MicroRNAs (miRNA) are ~20 nucleotide, noncoding RNAs that play an important role in posttranscriptional regulation for almost all genes. Unsurprisingly, miRNAs regulate junction protein gene expression and control junction structure integrity. In contrast, abnormal miRNA regulation of junction protein gene expression results in abnormal junction structure, causing related diseases. The major components of tight junctions include zonula occluden-1 (ZO-1), claudin-1, claudin-5, and occludin. The miRNA regulation of ZO-1 has been intensively investigated. ZO-1 and other tight junction proteins such as claudin-5 and occludin were positively regulated by miR-126, miR-107, and miR21 in different models. In contrast, ZO-1, claudin-5, and occludin were negatively regulated by miR-181a, miR-98, and miR150. Abnormal tight junction miRNA regulation accompanies cerebral middle artery ischemia, brain trauma, glioma metastasis, and so forth. The major components of adherens junctions include VE-cadherin, β-catenin, plakoglobin, P120, and vinculin. VE-cadherin and β-catenin were regulated by miR-9, miR-99b, miR-181a, and so forth. These regulations directly affect VE-cadherin-β-catenin complex stability and further affect embryo and tumor angiogenesis, vascular development, and so forth. miR-155 and miR-126 have been shown to regulate PECAM-1 and affect neutrophil rolling and EC junction integrity. In focal adhesion junctions, the major components are integrin β4, paxillin, and focal adhesion kinase (FAK). Integrin β4 has been regulated by miR-184, miR-205, and miR-9. Paxillin has been regulated by miR-137, miR-145, and miR-218 in different models. FAK has been regulated by miR-7, miR-138, and miR-135. Deregulation of miRNAs is caused by viral infections, tumorigenesis, and so forth. By regulation of posttranscription, miRNAs manipulate junction protein expression in all cellular processes and further determine cellular fate and development. Elucidation of these regulatory mechanisms will become a new alternative therapy for many diseases, such as cancers and inflammatory diseases.

We investigated the miRNA profiles of breast cancer stem cells (CSCs) and non-CSC tumor cells by miRNA microarray and determined the effect of altered miR-1 expression on proliferation and migration of breast CSCs. The potential targets of miR-1 in the Wnt/β-catenin signaling were characterized by bioinformatics analysis and luciferase assay. We found that 14 miRNAs were up-regulated and 13 were down-regulated in the ESA⁺CD44⁺CD24⁻lineage⁻ CSCs, related to ESA⁺CD44⁻CD24⁺lineage⁻ non-CSC tumor cells. The miR-1 expression was associated inversely with aggressiveness of breast cancers. Furthermore, enhanced miR-1 expression decreased the percentages of SKBR3/CSCs and miR-1 inhibition increased the percentages of MCF-7/CSCs. Enhanced miR-1 expression significantly reduced the Frizzled 7 and Tankyrase-2 (TNKS2)-regulated luciferase activity in 293T cells and decreased Frizzled 7, TNKS2, c-Myc, octamer-binding transcription factor 4 (Oct4) and Nanog expression and the ratios of nuclear to cytoplasmic β-catenin as well as β-catenin-dependent luciferase activity in breast CSCs in vitro. miR-1 inhibited proliferation, migration and wound healing of breast CSCs in vitro. Enhanced miR-1 expression inhibited the growth of implanted MCF-7/CSCs while miR-1 inhibition promoted the growth of implanted MCF-7/CSCs in vivo. Our data indicate that miR-1 down-regulates breast CSC stemness, proliferation and migration by targeting the Frizzled 7 and TNKS2 to inhibit the Wnt/β-catenin signaling.

• breast cancer stem cells
• miRNA profile

This is a systematic review of studies investigating the prognostic value of different microRNAs (miRs) in renal cell carcinoma (RCC). Twenty-seven relevant studies were identified, with a total of 2578 subjects. We found that elevated expression of miR-21, miR-1260b, miR-210, miR-100, miR-125b, miR-221, miR-630, and miR-497 was associated with a poor prognosis in RCC patients. Conversely, decreased expression of miR-106b, miR-99a, miR-1826, miR-215, miR-217, miR-187, miR-129–3p, miR-23b, miR-27b, and miR-126 was associated with a worse prognosis. We performed meta-analyses on studies to address the prognostic value of miR-21, miR-126, miR-210, and miR-221. This revealed that elevated miR-21 expression was associated with shorter overall survival (OS; hazard ratio [HR], 2.29; 95% confidence interval [CI], 1.28–4.08), cancer specific survival (CSS; HR, 4.16; 95% CI, 2.49–6.95), and disease free survival (DFS; HR, 2.15; 95% CI, 1.16–3.98). The decreased expression of miR-126 was associated with shorter CSS (HR, 0.35; 95% CI, 0.15–0.85), OS (HR, 0.45; 95% CI, 0.30–0.69), and DFS (HR 0.30; 95% CI, 0.18–0.50). Our comprehensive systematic review reveals that miRs, especially miR-21 and miR-126, could be promising prognostic markers and useful therapeutic targets in RCC.

• meta-analysis
• microRNA
• prognosis biomarker
• renal cell carcinoma
• survival

• Cell cycle
• Glioma
• Proliferation
• miR-370-3p
• β-catenin

• DNA methylation
• clear cell renal cell carcinoma (ccRCC)
• histone modification
• long noncoding RNA
• microRNA

As an actively renewable tissue, changes in skin architecture are subjected to the regulation of stem cells that maintain the population of cells responsible for the formation of epidermal layers. Stems cells retain their self-renewal property and express biomarkers that are unique to this population. However, differential regulation of the biomarkers can initiate the pathway of terminal cell differentiation. Although, pockets of non-clarity in stem cell maintenance and differentiation in skin still exist, the influence of epigenetics in epidermal stem cell functions and differentiation in skin homeostasis and wound healing is clearly evident. The focus of this review is to discuss the epigenetic regulation of confirmed and probable epidermal stem cell biomarkers in epidermal stratification of normal skin and in diseased states. The role of epigenetics in wound healing, especially in diseased states of diabetes and cancer, will also be conveyed.

• biomarkers
• epidermal stem cells
• epigenetics
• microRNA
• skin
• wound healing

MicroRNAs (miRs) are small noncoding RNAs that govern many biological processes. They frequently acquire a gain or a loss of function in cancer and hence play a causative role in the development and progression of neoplasms. They could be used as biomarkers to improve our knowledge on diagnosis, prognosis and drug resistance, and to attempt therapeutic approaches in several types of cancer including clear cell renal cell carcinoma (ccRCC). ccRCC is the most predominant subtype of RCC that accounts for about 90% of all renal cancers. Since ccRCC is generally asymptomatic until very late, it is difficult to diagnose early. Moreover, in the absence of preventive treatments for metastatic ccRCC after surgical resection of the primary cancer, predictive prognostic biomarkers are needed in order to achieve appropriate therapies. Herein the role of miRs in the biology of ccRCC and the potential applications of these molecules are discussed. Moreover, future applications in the diagnostic and prognostic field, as well as their impact on drug response and therapeutic targets are also explored. Their use in clinical practice as molecular biomarkers alone, or in combination with other biological markers could accelerate progress, help design personalized therapies, limit side effects, and improve quality of life of ccRCC patients.

• MAP2K1
• Non-small cell lung cancer (NSCLC)
• invasion
• miR-449a

• Cancer
• Non-canonical Wnt signaling
• Post-transcriptional regulation
• Regulatory network
• β-catenin

• Diabetes Mellitus/genetics
• Diabetes Mellitus/pathology
• Embryonic Development
• Heart Diseases/genetics
• Heart Diseases/pathology
• Humans
• MicroRNAs/metabolism
• Neoplasms/genetics
• Neoplasms/pathology
• Urinary Bladder Diseases/genetics
• Urinary Bladder Diseases/pathology
• Wnt Signaling Pathway

• P20 GM103446 NIGMS NIH HHS
• P20 GM103653 NIGMS NIH HHS
• 5P20GM103653-02 NIGMS NIH HHS

• breast cancer
• cancer stem cells
• signalling pathways

• Apoptosis
• Clear cell renal cell carcinoma
• MicroRNA-185
• Proliferation
• VEGFA
• VHL

Despite recent advances in the understanding of the biology of renal cell carcinoma (RCC), successful surgical treatment and implementation of novel-targeted therapies, the prognosis for RCC patients remains poor. Late presentation, tumor heterogeneity and in particular the lack of molecular biomarkers for early detection, classification and the surveillance of RCC treatments are major obstacles. The increasing knowledge regarding the functional role of microRNAs (miRNAs) in pathophysiological processes may provide an important link to the identification of suitable therapeutic targets and diagnostic/prognostic biomarkers for RCC. The aim of this review was to provide new insight into the function of miRNAs in the pathogenesis of RCC and to emphasize their potential as diagnostic and prognostic markers, as well as therapeutic targets.

Cardiovascular diseases and cancers are the leading causes of morbidity and mortality in the world. MicroRNAs (miRNAs) are short non-coding RNAs that primarily repress target mRNAs. Here, miR-24, miR-125b, miR-195, and miR-214 were selected as representative cardio-miRs that are upregulated in human heart failure. To bridge the gap between miRNA studies in cardiology and oncology, the targets and functions of these miRNAs in cardiovascular diseases and cancers will be reviewed. ACVR1B, BCL2, BIM, eNOS, FGFR3, JPH2, MEN1, MYC, p16, and ST7L are miR-24 targets that have been experimentally validated in human cells. ARID3B, BAK1, BCL2, BMPR1B, ERBB2, FGFR2, IL6R, MUC1, SITR7, Smoothened, STAT3, TET2, and TP53 are representative miR-125b targets. ACVR2A, BCL2, CCND1, E2F3, GLUT3, MYB, RAF1, VEGF, WEE1, and WNT7A are representative miR-195 targets. BCL2L2, ß-catenin, BIM, CADM1, EZH2, FGFR1, NRAS, PTEN, TP53, and TWIST1 are representative miR-214 targets. miR-125b is a good cardio-miR that protects cardiomyocytes; miR-195 is a bad cardio-miR that elicits cardiomyopathy and heart failure; miR-24 and miR-214 are bi-functional cardio-miRs. By contrast, miR-24, miR-125b, miR-195, and miR-214 function as oncogenic or tumor suppressor miRNAs in a cancer (sub)type-dependent manner. Circulating miR-24 is elevated in diabetes, breast cancer and lung cancer. Circulating miR-195 is elevated in acute myocardial infarction, breast cancer, prostate cancer and colorectal adenoma. Circulating miR-125b and miR-214 are elevated in some cancers. Cardio-miRs and onco-miRs bear some similarities in functions and circulation profiles. miRNAs regulate WNT, FGF, Hedgehog and other signaling cascades that are involved in orchestration of embryogenesis and homeostasis as well as pathogenesis of human diseases. Because circulating miRNA profiles are modulated by genetic and environmental factors and are dysregulated by genetic and epigenetic alterations in somatic cells, circulating miRNA association studies (CMASs) within several thousands of cases each for common non-cancerous diseases and major cancers are necessary for miRNA-based diagnostics.

• Alzheimer's disease
• early diagnosis
• gastric cancer
• hypertension
• pancreatic cancer
• personalize medicine
• rheumatoid arthritis
• stem cells

Emerging evidence has suggested that dysregulation of miR-182-5p may contribute to tumor development and progression in several types of human cancers. However, its role in renal cell carcinoma (RCC) is still unknown.

Quantitative RT-PCR was used to quantify miR-182-5p expression in RCC clinical tissues. Bisulfite sequencing PCR was used for DNA methylation analysis. The CCK-8, colony formation, flow cytometry, and a xenograft model were performed. Immunohistochemistry was conducted using the peroxidase and DAB methods. A miR-182-5p target was determined by luciferase reporter assays, quantitative RT-PCR, and Western blotting.

miR-182-5p is frequently down-regulated in human RCC tissues. Epigenetic modulation may be involved in the regulation of miR-182-5p expression. Enforced expression of miR-182-5p in RCC cells significantly inhibited the proliferation and tumorigenicity in vitro and in vivo. Additionally, overexpression of miR-182-5p induced G1-phase arrest via inhibition of AKT/FOXO3a signaling. Moreover, FLOT1 was confirmed as a target of miR-182-5p. Silencing FLOT1 by small interfering RNAs phenocopied the effects of miR-182-5p overexpression, whereas restoration of FLOT1 in miR-182-5p -overexpressed RCC cells partly reversed the suppressive effects of miR-182-5p.

These findings highlight an important role for miR-182-5p in the pathogenesis of RCC, and restoration of miR-182-5p could be considered as a potential therapeutic strategy for RCC therapy.

• APC
• Adenomatous polyposis coli
• CK1α
• Casein kinase 1α
• DKK
• Dickkop
• Disheveled
• Dvl
• EZH2
• FZD
• Frizzled
• GSK3β
• Glycogen synthase kinase 3β
• HCC
• Hepatocellular carcinoma
• IRS
• Insulin receptor substrate
• LDL receptor–related protein
• LEF
• LRP
• Lymphoid enhancer-binding factor
• NLK
• Nemo-like kinase
• Neoplasm
• Secreted frizzled-related proteins
• T-cell factor
• TCF
• WIF
• Wnt inhibitory factor
• Wnt/β-catenin signaling
• Wnt–microRNA regulatory network
• Zeste homologue 2
• miRs
• microRNA
• microRNAs
• sFRPs

• Adaptor Proteins, Signal Transducing/biosynthesis
• Adult
• Animals
• Biomarkers, Tumor/metabolism
• Cadherins/biosynthesis
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/pathology
• Cell Line, Tumor
• Epithelial-Mesenchymal Transition
• Female
• Forkhead Transcription Factors/biosynthesis
• Gene Expression Regulation, Neoplastic
• Hepatitis B, Chronic/physiopathology
• Humans
• Liver/metabolism
• Liver Neoplasms/genetics
• Liver Neoplasms/pathology
• Lung Neoplasms/secondary
• Male
• Mice
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Metastasis/genetics
• Neoplasm Metastasis/physiopathology
• Neoplasm Recurrence, Local/physiopathology
• Phosphoproteins/biosynthesis
• Prognosis
• Snail Family Transcription Factors
• Transcription Factors/biosynthesis
• Transcriptional Activation
• beta Catenin/metabolism

• cancer stem cells
• epigenetics
• dna methylation
• histone modifications
• micrornas

• Animals
• DNA/genetics
• DNA/metabolism
• DNA Methylation
• Epigenesis, Genetic
• Gene Expression Regulation, Neoplastic
• Histones/genetics
• Histones/metabolism
• Humans
• Neoplasms/genetics
• Neoplasms/metabolism
• Neoplasms/pathology
• Neoplastic Stem Cells/metabolism
• Neoplastic Stem Cells/pathology
• Signal Transduction

• Animals
• Genes, Tumor Suppressor
• Humans
• MicroRNAs/genetics
• Neoplasms/genetics
• Neoplasms/therapy
• Oncogenes/genetics