• Endometrial epithelial cells
• Exosomes
• Human umbilical cord mesenchymal stem cells
• Signal transducer and activator of transcription 3
• Ubiquitin protein ligase E3C
• miR-137-3p

• Circular RNA
• HOTAIR-miR-34a-5p
• Hepatocellular carcinoma
• Long non-coding RNA
• Metastasis
• MicroRNA

• Humans
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/metabolism
• Liver Neoplasms/genetics
• Liver Neoplasms/pathology
• Liver Neoplasms/metabolism
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Neoplasm Metastasis
• Gene Expression Regulation, Neoplastic
• Epithelial-Mesenchymal Transition
• Animals
• RNA, Long Noncoding/genetics

• Cancer
• Cell biology
• Molecular biology

• LncRNA AC007207.2
• miRNA
• osteosarcoma

This study aims at uncovering the effects of microRNAs (miRNAs) on the F8 gene and FVIII protein in hemophilia A (HA).

F8-targeting miRNAs were predicted by TargetScan, miRDB, and starBase. MiRNAs, predicted by at least two of the three databases, were selected for further study, and their expressions in the blood of HA patients without F8 mutations and healthy controls were detected. A dual-luciferase reporter assay was performed to verify the binding between hsa-miR-5581-3p/hsa-miR-542-3p and F8. In addition, the regulation of F8 by hsa-miR-5581-3p/hsa-miR-542-3p was investigated in human umbilical vein endothelial cells (HUVECs) and lymphoblastoid cell line (LCL) that displayed endogenous expression of FVIII. qRT-PCR was used to detect the expressions of miRNAs and F8 gene, and Western blotting was conducted to measure the expression of FVIII protein.

A total of 42 F8-targeting miRNAs were predicted by at least two of the three databases. Among these miRNAs, hsa-miR-5581-3p and hsa-miR-542-3p were highly expressed in the blood of HA patients and have not been reported in previous studies of HA. Both hsa-miR-5581-3p and hsa-miR-542-3p could bind the 3′UTR of F8 mRNA. Upregulation of hsa-miR-5581-3p or hsa-miR-542-3p suppressed the expressions of F8 mRNA and FVIII protein in HUVECs and LCL cells.

Hsa-miR-5581-3p and hsa-miR-542-3p target the F8 gene and suppress the expression of FVIII protein, which may contribute to the development of HA without F8 mutations.

• F8 gene
• FVIII
• Hemophilia A
• Hsa-miR-542-3p
• Hsa-miR-5581-3p

Bone metastases cause substantial morbidity and implicate worse clinical outcomes for clear-cell renal cell carcinoma patients. MicroRNAs are small RNA molecules that modulate gene translation and are involved in the development of cancer and metastasis. We identified six microRNAs that are potentially specifically involved in metastasis to bone, of which two seem protective and four implicate a higher risk. This aids further understanding of the process of metastasizing to bone. Furthermore, these microRNA hold potential for biomarkers or therapeutic targets.

Bone metastasis in clear-cell renal cell carcinoma (ccRCC) leads to substantial morbidity through skeletal related adverse events and implicates worse clinical outcomes. MicroRNAs (miRNA) are small non-protein coding RNA molecules with important regulatory functions in cancer development and metastasis. In this retrospective analysis we present dysregulated miRNA in ccRCC, which are associated with bone metastasis. In particular, miR-23a-3p, miR-27a-3p, miR-20a-5p, and miR-335-3p specifically correlated with the earlier appearance of bone metastasis, compared to metastasis in other organs. In contrast, miR-30b-3p and miR-139-3p were correlated with less occurrence of bone metastasis. These miRNAs are potential biomarkers and attractive targets for miRNA inhibitors or mimics, which could lead to novel therapeutic possibilities for bone targeted treatment in metastatic ccRCC.

• SATB2
• bone metastasis
• miR-139-3p
• miR-20a-5p
• miR-23a-3p
• miR-27a-3p
• miR-30b-3p
• miR-335-3p
• microRNA
• renal cell carcinoma

• Cancer
• E3 ubiquitin ligase
• Posttranslational modification
• Protein Degradation
• Ubiquitination
• “Other” subfamily HECT

• Biomarkers
• HCC
• HCV
• miR-221
• miR-542
• qRT-PCR

Breast cancer (BrCa) is the most common female malignancy worldwide and has the highest morbidity among all cancers in females. Unfortunately, the mechanisms of BrCa growth and metastasis, which lead to a poor prognosis in BrCa patients, have not been well characterized.

Immunohistochemistry (IHC) was performed on a BrCa tissue microarray (TMA) containing 80 samples to evaluate ubiquitin protein ligase E3C (UBE3C) expression. In addition, a series of cellular experiments were conducted to reveal the role of UBE3C in BrCa.

In this research, we identified UBE3C as an oncogenic factor in BrCa growth and metastasis for the first time. UBE3C expression was upregulated in BrCa tissues compared with adjacent breast tissues. BrCa patients with high nuclear UBE3C expression in tumors showed remarkably worse overall survival (OS) than those with low nuclear expression. Knockdown of UBE3C expression in MCF-7 and MDA-MB-453 BrCa cells inhibited cell proliferation, migration and invasion in vitro, while overexpression of UBE3C in these cells exerted the opposite effects. Moreover, UBE3C promoted β-catenin nuclear accumulation, leading to the activation of the Wnt/β-catenin signaling pathway in BrCa cells.

Collectively, these results imply that UBE3C plays crucial roles in BrCa development and progression and that UBE3C may be a novel target for the prevention and treatment of BrCa.

• Breast cancer
• Cancer progression
• UBE3C
• β-catenin

• Hepatocellular carcinoma
• OIP5-AS1
• WNT pathway
• YY1
• miR-300

• AGO1
• Epithelial-mesenchymal transition
• Renal fibrosis
• miR-542-3p

• Animals
• Argonaute Proteins/genetics
• Binding Sites
• Cell Line
• Computational Biology
• Disease Models, Animal
• Eukaryotic Initiation Factors/genetics
• Fibrosis
• Glucose/metabolism
• Humans
• Kidney/pathology
• Kidney Diseases/genetics
• Kidney Diseases/pathology
• Male
• MicroRNAs/genetics
• Rats
• Rats, Sprague-Dawley
• Ureteral Obstruction/pathology

This study aimed to investigate the effect and mechanism of miR-26a-5p on proliferation and apoptosis of hepatocellular carcinoma (HCC) cells.

RT-PCR was used to analyze the expression of miR-26a-5p in HCC cells and its targeted gene HMGA2 mRNA determined by biological information prediction. The rate of proliferation, invasion, apoptosis, and expression levels of related proteins of HCC cells overexpressing miR-26a-5p or those after knocking down HMGA2 expression were detected by MTT, invasion and apoptosis rate tests. Moreover, the apoptosis-promoting protein bax was upregulated and the anti-apoptosis-related protein Bcl-2 was downregulated.

RT-qPCR results showed that the level of miR-26a-5p was downregulated in HCC tissues and cells, and the expression of HMGA2 was upregulated; besides, the expression of miR-26a-5p and HMGA2 was negatively correlated; miR-26a-5p was correlated with tumor diameter, differentiation degree, TNM staging and lymph node metastasis. Cell tests confirmed that miR-26a-5p functioned in tumor suppression, including inhibiting cell proliferation and invasion in two hepatocellular carcinoma cell lines and promoting apoptosis. Bioinformatics prediction and subsequent experiments proved that HMGA2 was the direct target of miR-26a-5p; moreover, after knocking down HMGA2 expression in HCC cells, cell proliferation and invasion ability were significantly inhibited, and apoptosis rate increased significantly.

miR-26a-5p can inhibit the proliferation and invasion of HCC cells and promote their apoptosis by directly targeting HMGA2. Abnormal decrease of miR-26a-5p and increase of its target HMGA2 are important factors that may participate in the occurrence and development of HCC. miR-26a-5p may be a new potential target for its treatment.

• apoptosis
• hepatocellular carcinoma cells
• mechanism research
• miR-26a-5p
• proliferation

• ctDNA
• hepatocellular carcinoma
• lncRNA
• miRNA
• noncoding RNA
• therapy

Aging is believed to have a close association with cardiovascular diseases, resulting in various pathological alterations in blood vessels, including vascular cell phenotypic shifts. In aging vessels, the microRNA(miRNA)-mediated mechanism regulating the vascular smooth muscle cell (VSMC) phenotype remains unclarified. MiRNA microarray was used to compare the expressions of miRNAs in VSMCs from old rats (oVSMCs) and young rats (yVSMCs). Quantitative reverse transcription real-time PCR (qRT-PCR) and small RNA transfection were used to explore the miR-542-3p expression in oVSMCs and yVSMCs in vitro. Calcification induction of yVSMCs was conducted by the treatment of β-glycerophosphate (β-GP). Alizarin red staining was used to detect calcium deposition. Western blot and qRT-PCR were used to investigate the expression of the smooth muscle markers, smooth muscle 22α (SM22α) and calponin, and the osteogenic markers, osteopontin (OPN), and runt-related transcription factor 2 (Runx2). Lentivirus was used to overexpress miR-542-3p and bone morphogenetic protein 7 (BMP7) in yVMSCs. Luciferase reporter assay was conducted to identify the target of miR-542-3p.

Compared with yVSMCs, 28 downregulated and 34 upregulated miRNAs were identified in oVSMCs. It was confirmed by qRT-PCR that oVSMC expressed four times lower miR-542-3p than yVSMCs. Overexpressing miR-542-3p in yVSMCs suppressed the osteogenic differentiation induced by β-GP. Moreover, miR-542-3p targets BMP7 and overexpressing BMP7 in miR-542-3p–expressing yVSMCs reverses miR-542-3p’s inhibition of osteogenic differentiation.

miR-542-3p regulates osteogenic differentiation of VSMCs through targeting BMP7, suggesting that the downregulation of miR-542-3p in oVSMCs plays a crucial role in osteogenic transition in the aging rat.

• Aging
• Mir-542-3p
• Osteogenic differentiation
• Vascular smooth muscle cells

• Autophagy
• Aβ-degrading proteases
• BBB transporters
• Heat shock proteins
• Phagocytosis
• Ubiquitin–proteasome system
• microRNAs

• BTG3
• HCC
• Tumor growth
• Tumor metastasis
• miR-519c-3p

• DAB2IP
• HCC
• Tumor growth
• Tumor metastasis
• miR-1307-3p

• MAPK
• ZNF418
• c-Jun
• hepatocellular carcinoma
• miR-1204

Most cancer deaths are due to metastasis, and almost all cancers have their preferential metastatic organs, known as “organotropism metastasis”. Epithelial-mesenchymal plasticity has been described as heterogeneous and dynamic cellular differentiation states, supported by emerging experimental evidence from both molecular and morphological levels. Many molecular factors regulating epithelial-mesenchymal plasticity have tissue-specific and non-redundant properties. Reciprocally, cellular epithelial-mesenchymal plasticity contributes to shaping organ-specific pre-metastatic niche (PMN) including distinct local immune landscapes, mainly through secreted bioactive molecular factors. Here, we summarize recent progress on the involvement of tumor epithelial-mesenchymal plasticity in driving organotropic metastasis and regulating the function of different immune cells in organ-specific metastasis.

• EMT heterogeneity
• cell–cell communication
• organotropism metastasis
• tumor immune escape

Recently, aberrant expression of miR‐876‐5p has been reported to participate in the progression of several human cancers. However, the expression and function of miR‐876‐5p in osteosarcoma (OS) are still unknown. Here, we found that the expression of miR‐876‐5p was significantly down‐regulated in OS tissues compared to para‐cancerous tissues. Clinical association analysis indicated that underexpression of miR‐876‐5p was positively correlated with advanced clinical stage and poor differentiation. More importantly, OS patients with low miR‐876‐5p level had a significant shorter overall survival compared to miR‐876‐5p high‐expressing patients. In addition, gain‐ and loss‐of‐function experiments demonstrated that miR‐876‐5p restoration suppressed whereas miR‐876‐5p knockdown promoted cell proliferation, migration and invasion in both U2OS and MG63 cells. In vivo studies revealed that miR‐876‐5p overexpression inhibited tumour growth of OS in mice. Mechanistically, miR‐876‐5p reduced c‐Met abundance in OS cells and inversely correlated c‐Met expression in OS tissues. Herein, c‐Met was recognized as a direct target of miR‐876‐5p using luciferase reporter assay. Notably, c‐Met restoration rescued miR‐876‐5p attenuated the proliferation, migration and invasion of OS cells. In conclusion, these findings indicate that miR‐876‐5p may be used as a potential therapeutic target and promising biomarker for the diagnosis and prognosis of OS.

• c-Met
• metastasis
• miR-876-5p
• osteosarcoma
• proliferation

Our goal was to explore the function of miR‐552 and its potential target AJAP1 in hepatocellular carcinoma (HCC) oncogenesis and progression. In this study, bioinformatics analysis was performed to detect abnormally expressed miRNAs. The relationship between miR‐552 and AJAP1 was validated using luciferase reporter assays. RT‐qPCR and Western blot assays were applied to explore the expression level of miR‐552, AJAP1 and epithelial‐mesenchymal transition (EMT) markers. HCC cell proliferation was examined using CCK8 assays, while migration and invasion were investigated using Transwell assays. Nude mouse tumourigenesis models were established to facilitate observation of HCC progression in vivo. Finally, prognostic analysis was performed to discover how the prognosis of HCC patients correlated with miR‐552 and AJAP1 expression. MiR‐552 overexpression in HCC cells promoted HCC cell migration, invasion and EMT by targeting/suppressing AJAP1. Poorer prognosis appeared in HCC patients with higher miR‐552 expression or lower AJAP1 levels. Our findings suggested that miR‐552 promotes HCC oncogenesis and progression by inhibiting AJAP1 expression.

• EMT
• AJAP1
• hepatocellular carcinoma
• miR-552

Osteosarcoma (OS) is the most common pediatric primary bone tumor, with high malignancy rates and a poor prognosis following metastasis. At present, the role of microRNA (miR)-542-3p in OS remains to be elucidated. The purpose of the present study was to investigate the expression level of miR-542-3p in OS, and its potential molecular mechanisms, via a bioinformatics analysis. First, the expression of miR-542-3p in OS based on the continuous variables of the Gene Expression Omnibus database and PubMed was studied. Subsequently, the potential target genes of miR-542-3p were predicted using gene expression profiles and bioinformatics software. On the basis of the Database for Annotation, Visualization and Integrated Discovery, version 6.8, a study of gene ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway knowledge base was conducted to explore the biological value of miR-542-3p in OS. Finally, the protein-protein interaction (PPI) network was completed using the STRING database. The expression of miR-542-3p in OS was revealed to be significantly higher compared with that in normal tissue. In total, 1,036 target genes of miR-542-3p were obtained. The results of the GO enrichment analysis revealed that the significant terms were ‘bone development’, ‘cell cycle arrest’ and ‘intracellular signal transduction’. The results of the KEGG analysis revealed the highlighted pathways that were targeted to miR-542-3p, including the sphingolipid signaling pathway (P=3.91×10⁻⁵), the phosphoinositide 3-kinase (PI3K)-AKT serine/threonine kinase (AKT) signaling pathway (P=3.17×10⁻⁵) and the insulin signaling pathway (P=1.04×10⁻⁵). The PPI network revealed eight hub genes: Ubiquitin-60S ribosomal protein L40, Ras-related C3 botulinum toxin substrate, mitogen-activated protein kinase 1, epidermal growth factor receptor, cystic fibrosis transmembrane conductance regulator, PI3K regulatory subunit 1, AKT1, and actin-related protein 2/3 complex subunit 1A, which may be the key target genes of miR-542-3p in OS. Taken together, these results have demonstrated that miR-542-3p was overexpressed in OS. The potential target genes and biological functions of miR-542-3p may provide novel insights into the differentially expressed genes that are involved in OS.

• ERBB2IP
• Hepatocellular carcinoma
• KTN1-AS1
• Tumor growth
• miR-23c

• ARID2
• hepatocellular carcinoma
• invasion
• miR-376c-3p
• proliferation

• CTNND1
• Hepatocellular carcinoma
• Metastasis
• Tumor growth
• Wnt/β-catenin signaling
• microRNA-298

• Apoptosis
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/secondary
• Catenins/genetics
• Catenins/metabolism
• Cell Movement
• Cell Proliferation
• Cyclin D1/genetics
• Cyclin D1/metabolism
• Disease Progression
• G1 Phase Cell Cycle Checkpoints
• Gene Expression Regulation, Neoplastic
• Hep G2 Cells
• Humans
• Liver Neoplasms/genetics
• Liver Neoplasms/metabolism
• Liver Neoplasms/pathology
• Matrix Metalloproteinase 7/genetics
• Matrix Metalloproteinase 7/metabolism
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Neoplasm Invasiveness
• Time Factors
• Wnt Proteins/genetics
• Wnt Proteins/metabolism
• Wnt Signaling Pathway
• beta Catenin/genetics
• beta Catenin/metabolism
• Delta Catenin

miR-490-3p could play vital roles in multiple cancers. However, the role of miR-490-3p in hepatocellular carcinoma (HCC) remains uncertain. In this study, we sought to explore the underlying role of miR-490-3p in HCC.

In this study, we explored the clinical role of miR-490-3p in HCC via quantitative reverse transcription–polymerase chain reaction (RT-qPCR) and The Cancer Genome Atlas (TCGA) database. Then, a meta-analysis was performed to evaluate the expression trend and diagnostic value of miR-490-3p in HCC. Furthermore, 12 miRNA prediction algorithms were applied to predict the potential target genes of miR-490-3p. The differentially expressed genes in HCC in the Gene Expression Profiling Interactive Analysis (GEPIA) database were also selected. Additionally, bioinformatics analyses were utilized to investigate the possible functions and pathways of the target genes.

miR-490-3p was clearly down-regulated in HCC based on RT-qPCR (P=0.002). Consistent with the results of RT-qPCR, miR-490 was more highly expressed in normal liver tissue than in HCC (P<0.001). Additionally, the meta-analysis confirmed the results from RT-qPCR and TCGA. Furthermore, based on the prediction algorithms and GEPIA, a total of 113 genes were selected. According to the bioinformatics analyses, we found that the most remarkably enriched functional terms included protein transport, poly(A) RNA binding, and intracellular organelle part. Additionally, the miR-490-3p target genes were significantly related to the pathways in cancer.

We found that miR-490-3p is down-regulated in HCC and is related to genes that have potential tumoral functions. However, the exact mechanism should be confirmed by functional experiments.

MicroRNAs (miRNAs) have been recognized as key regulators of tumorigenesis and progression. Serum miR-302c-3p expression is prominently deregulated in HCV-related hepatocellular carcinoma (HCC). However, the expression of miR-302c-3p and its functional role in HBV-related HCC are rarely investigated. In this study, we found that the expression levels of miR-302c-3p were prominently down-regulated in HCC tissues compared to matched tumor-adjacent tissues. Moreover, miR-302c-3p under-expression was detected in HCC cell lines compared to a normal hepatic cell line LO2. Low miR-302c-3p expression was positively correlated with multiple tumor nodes, venous infiltration and advanced TNM tumor stage of HCC patients. Notably, our follow up data and TCGA data demonstrated that low miR-302c-3p expression predicted a poor survival of HCC patients. Functionally, miR-302c-3p overexpression inhibited migration and invasion of MHCC97H cells in vitro. Additionally, miR-302c-3p knockdown showed an opposite effect on these metastatic behaviors of HepG2 cells. MiR-302c-3p negatively regulated tumor necrosis factor receptor associated factor 4 (TRAF4) abundance by directly targeting 3'-UTR of TRAF4 mRNA. The expression of TRAF4 was up-regulated in HCC tissues. The level of TRAF4 mRNA was inversely correlated with miR-302c-3p expression in HCC specimens. Mechanistically, miR-302c-3p restrained AKT-mediated epithelial-mesenchymal transition (EMT) in HCC cells. Importantly, TRAF4 restoration reversed the inhibitory effect of miR-302c-3p on AKT-induced EMT and HCC cell metastasis. MK2206, an AKT inhibitor, inhibited miR-302c-3p knockdown-induced EMT in HepG2 cells. In summary, these results indicate that miR-302c-3p exhibits a tumor suppressive role in HCC by targeting TRAF4. Inhibition of miR-302c-3p/TRAF4 axis may serve as a therapeutic target for HCC.

• EMT, metastasis
• TRAF4
• hepatocellular carcionoma
• miR-302c-3p

• Colorectal cancer
• Epithelial-mesenchymal transition, tumor metastasis
• Transcription factor AP4
• miR-302c

MicroRNAs (miRNAs) are involved in cancer genesis and progression via acting as tumor suppressors or oncogenes. Previous studies report that miR-1296 shows upregulation in both colorectal cancer (CRC) tissues and plasma samples. However, the accurate clinical significance of miR-1296 and its role in CRC have not been well investigated. The aim of the present study was to disclose the aberrant expression, clinical significance, and the relevant biological function of miR-1296 in CRC. We found a marked upregulation of miR-1296 expression in CRC tissues compared to tumor-adjacent tissues. MiR-1296 overexpression was detected in five CRC cell lines (HCT116, Caco2, HT29, SW620 and SW480). High miR-1296 level was remarkably correlated with tumor size (>5cm), lymph node metastasis and TNM stage (III+IV). Notably. High miR-1296 expression was identified as a predictive factor for poor prognosis of CRC patients by survival analysis. MiR-1296 knockdown inhibited proliferation, migration, invasion capacities of HCT116 and SW480 cells in vitro. Moreover, miR-1296 silencing restrained the growth of CRC cells in vivo. Splicing factor proline and glutamine rich (SFPQ), a novel RNA binding protein, was identified as a direct target gene of miR-1296 in CRC. Downregulation of SFPQ expression was inversely associated with miR-1296 expression in CRC tissues. The Cancer Genome Atlas (TCGA) data revealed the prognostic value of dysregulated SFPQ in CRC patients. Interestingly, our findings established that the oncogenic role of miR-1296 was at least partially mediated by SFPQ in CRC cells. Collectively, these data indicate that miR-1296 accelerates CRC progression possibly by targeting SFPQ and may serve as a potential predictive factor and therapeutic target for CRC.

• Colorectal cancer
• Metastasis
• SFPQ
• Tumor growth
• microRNA-1296

• BCORL1
• EMT
• Hepatocellular carcionoma
• Tumor metastasis
• miR-876-5p

Lung cancer is a devastating disease with overall bleak prognosis. Current methods to diagnose lung cancer are rather invasive and are inadequate to detect the disease at an early stage when treatment is likely to be most effective. In this study, a shotgun sequencing approach was used to study the microRNA (miRNA) cargo of serum-derived exosomes of small cell lung cancer (SCLC) (n=9) and non-small cell lung cancer (NSCLC) (n=11) patients, and healthy controls (n=10). The study has identified 17 miRNA species that are differentially expressed in cancer patients and control subjects. Furthermore, within the patient groups, a set of miRNAs were differentially expressed in exosomal samples obtained before and after chemotherapy treatment. This manuscript demonstrates the potential of exosomal miRNAs for developing noninvasive tests for disease differentiation and treatment monitoring in lung cancer patients.

• NSCLC
• SCLC
• exosome
• liquid biopsy
• miRNA

• FBXO11
• Hepatocellular carcionoma
• Metastasis
• Proliferation
• miR-26a

• Cell proliferation
• Hepatocellular carcinoma
• Survivin
• Tumor growth
• microRNA-542-3p

• 3' Untranslated Regions
• HEK293 Cells
• Humans
• MicroRNAs/physiology
• Microtubule Proteins/metabolism
• Nuclear Proteins/metabolism
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Transcription Factors/metabolism
• Ubiquitin-Protein Ligases

Cancer metastasis is a malignant process by which tumor cells migrate from their primary site of origin to other organs. It is the main cause of poor prognosis in cancer patients. Angiogenesis is the process of generating new blood capillaries from pre-existing vasculature. It plays a vital role in primary tumor growth and distant metastasis. MicroRNAs are small non-coding RNAs involved in regulating normal physiological processes as well as cancer pathogenesis. They suppress gene expression by specifically binding to the 3′-untranslated region (3′-UTR) of their target genes. They can thus act as oncogenes or tumor suppressors depending on the function of their target genes. MicroRNAs have shown great promise for use in anti-metastatic cancer therapy. In this article, we review the roles of various miRNAs in cancer angiogenesis and metastasis and highlight their potential for use in future therapies against metastatic cancer.

• angiogenesis
• cancer
• metastasis
• microRNAs
• therapy

Recent studies have reported that microRNA-526b (miR-526b) is implicated in the growth and metastasis of cancer cells. However, the clinical significance of miR-526b and its role as well as underlying mechanisms are largely unknown in hepatocellular carcinoma (HCC). Here, we detected miR-526b expression difference between HCC and matched nontumor tissues with qRT-PCR. We found that miR-526b displayed lower expression in HCC patient tissues and cells. Clinical analysis revealed that low miR-526b expression correlated with large tumor size, venous infiltration, advanced tumor-node-metastasis (TNM) stage. Furthermore, miR-526b underexpression independently predicted poor prognosis of HCC patients. Functionally, we demonstrated that miR-526b inhibited proliferation, migration and invasion of HCC cells in vitro. Moreover, miR-526b overexpression restrained the tumor growth and pulmonary metastasis in vivo. Mechanistically, we proved that miR-526b could directly bind to 3′UTR of sirtuin 7 (SIRT7) mRNA and repressed its expression. miR-526b and SIRT7 showed a negative correlation in HCC tissues. More importantly, up-regulating SIRT7 expression antagonized miR-526b-inhibited proliferation, migration and invasion in SMMC-7721 cells. Furthermore, miR-526b suppressed epithelial-to-mesenchymal transition (EMT) of HCC cells. Immunoblotting analysis indicated that miR-526b reduced the levels of phosphorylated ERK (p-ERK), c-Myc, Cyclin D1, c-Jun, SNAIL and SLUG in HCC cells. SIRT7 restoration promoted phosphorylation of ERK and EMT in miR-526b overexpressing SMMC-7721 cells. Taken together, this is the first time we demonstrated that miR-526b might function as a prognostic biomarker and suppressed SIRT7 expression, and subsequently led to the growth and metastasis of HCC. Our findings provide miR-526b/SIRT7 axis as a promising drug target for HCC.

• HCC
• SIRT7
• metastasis
• miR-526b
• tumor growth

• EMT
• FTSJ2
• NSCLC
• Up-regulated
• miR-542-3p