• Drug resistance
• Glioblastoma
• KH RNA binding domain containing, signal transduction associated 3
• Proteomics
• Temozolomide

• Temozolomide/pharmacology
• Glioblastoma/pathology
• Glioblastoma/drug therapy
• Glioblastoma/genetics
• Glioblastoma/metabolism
• Humans
• Drug Resistance, Neoplasm
• Neoplastic Stem Cells/metabolism
• Neoplastic Stem Cells/drug effects
• Neoplastic Stem Cells/pathology
• Antineoplastic Agents, Alkylating/pharmacology
• Cell Line, Tumor
• Cell Proliferation/drug effects
• Cell Self Renewal/drug effects
• Brain Neoplasms/pathology
• Brain Neoplasms/drug therapy
• Brain Neoplasms/metabolism
• Brain Neoplasms/genetics
• Dacarbazine/pharmacology
• Dacarbazine/analogs & derivatives
• RNA-Binding Proteins/metabolism
• RNA-Binding Proteins/genetics
• Gene Expression Regulation, Neoplastic/drug effects
• Cell Movement/drug effects

• Neuroinflammation
• glioblastoma
• glioma
• inflammation
• miRNA
• microRNA
• non-coding RNA
• oncogene
• oncomir
• schizophrenia
• tumor suppressor

• Metadherin
• Miat
• long noncoding RNA
• medulloblastoma

• Carcinogenesis/genetics
• Carcinogenesis/metabolism
• Cerebellar Neoplasms/genetics
• Cerebellar Neoplasms/pathology
• Humans
• Medulloblastoma/genetics
• Medulloblastoma/pathology
• Membrane Proteins/genetics
• Membrane Proteins/metabolism
• MicroRNAs/genetics
• MicroRNAs/metabolism
• RNA, Long Noncoding/metabolism
• RNA-Binding Proteins/genetics
• RNA-Binding Proteins/metabolism

• P30 CA008748 NCI NIH HHS
• R35 GM124909 NIGMS NIH HHS
• S10 OD010598 NIH HHS

• brain tumour
• medulloblastoma
• miRNA
• stem cells
• subgroups

• biomarkers
• competing endogenous RNA network
• hepatocellular carcinoma
• immune infiltration
• prognostic prediction model

• Dicer1
• ETMR
• homeostasis
• neuroepithelium
• rosette
• telencephalic development

• Algorithms
• Computational Biology/methods
• DNA Copy Number Variations/genetics
• Databases, Genetic
• Decision Trees
• Genome, Human/genetics
• High-Throughput Nucleotide Sequencing
• Humans
• Models, Statistical

Medulloblastoma (MB) is the most common pediatric brain tumor and a primary cause of cancer-related death in children. Until a few years ago, only clinical and histological features were exploited for MB pathological classification and outcome prognosis. In the past decade, the advancement of high-throughput molecular analyses that integrate genetic, epigenetic, and expression data, together with the availability of increasing wealth of patient samples, revealed the existence of four molecularly distinct MB subgroups. Their further classification into 12 subtypes not only reduced the well-characterized intertumoral heterogeneity, but also provided new opportunities for the design of targets for precision oncology. Moreover, the identification of tumorigenic and self-renewing subpopulations of cancer stem cells in MB has increased our knowledge of its biology. Despite these advancements, the origin of MB is still debated, and its molecular bases are poorly characterized. A major goal in the field is to identify the key genes that drive tumor growth and the mechanisms through which they are able to promote tumorigenesis. So far, only protein-coding genes acting as oncogenic drivers have been characterized in each MB subgroup. The contribution of the non-coding side of the genome, which produces a plethora of transcripts that control fundamental biological processes, as the cell choice between proliferation and differentiation, is still unappreciated. This review wants to fill this major gap by summarizing the recent findings on the impact of non-coding RNAs in MB initiation and progression. Furthermore, their potential role as specific MB biomarkers and novel therapeutic targets is also highlighted.

• long non-coding RNA
• medulloblastoma
• microRNA
• neuronal differentiation
• non-coding RNA
• pediatric tumors
• tumor subgroups

Triple-negative breast cancer (TNBC) is the most aggressive subtypes of breast cancer, which has few effective targeted therapies. Various sources of evidence confirm that microRNAs (miRNAs) contribute to the progression and metastasis of human breast cancer. However, the molecular mechanisms underlying the changes in miRNAs expression and the regulation of miRNAs functions have not been well clarified. In this study, we found that the expression of miR-30b-5p was upregulated in breast cancer tissues and breast cancer cell lines, compared to paracancer tissues and normal breast cell lines. Moreover, induced overexpression of miR-30b-5p promoted the MDA-MB-231 and HCC 1937 cell growth, migration, and invasion and reduced the cellular apoptosis. Further studies confirmed that miR-30b-5p could directly target ASPP2 and then activate the AKT signaling pathway. Our results suggested that miR-30b-5p could act as a tumor promoter in TNBC. The newly identified miR-30b-5p/ASPP2/AKT axis represents a novel therapeutic strategy for treating TNBC.

• CTHRC1
• EMT
• OVCAR3
• Ovarian cancer
• miR-30b-3p

• Adhesion
• Colorectal liver metastasis
• Invasion
• Migration
• Mobility

• Biomarkers
• Breast cancer
• Metastasis
• MicroRNAs

• biomarker
• hypopharyngeal cancer
• miRNA
• score
• signature
• survival

Medulloblastoma, a central nervous system tumor that predominantly affects children, always requires aggressive therapy. Nevertheless, it frequently recurs as resistant disease and is associated with high morbidity and mortality. While recent efforts to subclassify medulloblastoma based on molecular features have advanced our basic understanding of medulloblastoma pathogenesis, optimal targets to increase therapeutic efficacy and reduce side effects remain largely undefined. Noncoding RNAs (ncRNAs) with known regulatory roles, particularly long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), are now known to participate in medulloblastoma biology, although their functional significance remains obscure in many cases. Here we review the literature on regulatory ncRNAs in medulloblastoma. In providing a comprehensive overview of ncRNA studies, we highlight how different lncRNAs and miRNAs have oncogenic or tumor suppressive roles in medulloblastoma. These ncRNAs possess subgroup specificity that can be exploited to personalize therapy by acting as theranostic targets. Several of the already identified ncRNAs appear specific to medulloblastoma stem cells, the most difficult-to-treat component of the tumor that drives metastasis and acquired resistance, thereby providing opportunities for therapy in relapsing, disseminating, and therapy-resistant disease. Delivering ncRNAs to tumors remains challenging, but this limitation is gradually being overcome through the use of advanced technologies such as nanotechnology and rational biomaterial design.

• Medulloblastoma
• circRNAs
• diagnostics therapeutics
• lncRNAs
• microRNAs

The existence of blood–tumor barrier (BTB) severely restricts the efficient delivery of antitumor drugs to cranial glioma tissues. Various strategies have been explored to increase BTB permeability. RNA-binding proteins and circular RNAs have recently emerged as potential regulators of endothelial cells functions. In this study, RNA-binding protein KH RNA-binding domain containing, signal transduction associated 3 (KHDRBS3) and circular RNA DENND4C (cDENND4C) were enriched in GECs. KHDRBS3 bound to cDENND4C and increased its stability. The knockdown of cDENND4C increased the permeability of BTB via downregulating the expressions of tight junction-related proteins. The miR-577 was lower expressed in GECs. The overexpressed miR-577 increased the permeability of BTB by reducing the tight junction-related protein expressions, and vice versa. Furthermore, cDENND4C acted as a molecular sponge of miR-577, which bound to miR-577 and inhibited its negative regulation of target genes ZO-1, occludin and claudin-1 to regulate BTB permeability. Single or combined treatment of KHDRBS3, cDENND4C, and miR-577 effectively promoted antitumor drug doxorubicin (DOX) across BTB to induce apoptosis of glioma cells. Collectively, the present study indicated that KHDRBS3 could regulate BTB permeability through the cDENND4C/miR-577 axis, which enhanced doxorubicin delivery across BTB. These findings may provide a novel strategy for chemotherapy of brain tumors.

Background: A wealth of evidence has shown that microRNAs (miRNAs) can modulate specific genes, increasing our knowledge on the fine-tuning regulation of protein expression. miR-221 and miR-222 have been frequently identified as deregulated across different cancer types; however, their prognostic significance in cancer remains controversial. In view of these considerations, we performed an updated systematic review and meta-analysis of published data investigating the effects of miR-221/222 on overall survival (OS) and other secondary outcomes among cancer patients. A systematic search of PubMed, Web of Knowledge, and Cochrane Library databases was performed. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were used to assess the strength of association. Results: Fifty studies, analyzing 6086 patients, were included in the systematic review. Twenty-five studies for miR-221 and 17 studies for miR-222 which assessed OS were included in the meta-analysis. High expression of miR-221 and miR-222 significantly predicted poor OS (HR: 1.48, 95% CI: 1.14–1.93, p = 0.003 and HR: 1.90, 95% CI: 1.43–2.54, p < 0.001, respectively). Subgroup analysis revealed that the finding on miR-221 was not as robust as the one on miR-222. Furthermore, high miR-222 expression was also associated with worse progression-free survival and disease-free survival pooled with recurrence-free survival. Conclusions: The meta-analysis demonstrated that high expression of miR-222 is associated with poor prognosis in cancer patients, whereas the significance of miR-221 remains unclear. More work is required to fully elucidate the role of miR-221 and miR-222 in cancer prognosis, particularly in view of the limitations of existing results, including the significant heterogeneity and limited number of studies for some cancers.

• cancer
• miR-221
• miR-222
• overall survival
• progression-free survival

The insulin-like growth factor 1 receptor (IGF1R) plays a vital role in immunomodulation and muscle and bone growth. The copy number variation (CNV) is believed to the reason for many complex phenotypic variations. In this paper, we statistically analyzed the copy number and the expression profiling in different tissue types of the IGF1R gene using the 422 samples from four Chinese beef cattle breeds, and the mRNA of IGF1R was widely expressed in nine tissue types of adult cattle (heart, liver, kidney, muscle, fat, stomach, spleen, lung and testis). Results of CNV and growth traits indicated that the IGF1R CNV was significantly associated with body weight and body height of Jinnan (JN) cattle and was significantly associated with body height and hucklebone width of Qinchuan (QC) cattle, making IGF1R CNV a promising molecular marker to improve meat production in beef cattle breeding. Bioinformatics predictions show that the CNV region is highly similar to the human genome, and there are a large number of transcription factors, DNase I hypersensitive sites, and high levels of histone acetylation, suggesting that this region may play a role in transcriptional regulation, providing directions for further study of the role of bovine CNV and economic traits.

• GNA13
• colorectal cancer
• initiation
• invasion
• microRNA-30d
• proliferation

Ricolinostat (ACY-1215), a first-in-class selective HDAC6 inhibitor, exhibits antitumor effects alone or in combination with other drugs in various cancers. However, its efficacy in esophageal cancer remains unclear. In this study, we found that the high expression of HDAC6 was associated with poor prognosis in esophageal squamous cell carcinoma (ESCC) tissues. Then, we identified that ACY-1215 significantly inhibited cellular proliferation in ESCC, and caused G2/M phase arrest and apoptosis. We further demonstrated that ACY-1215 treatment reduced the expression of PI3K, P-AKT, P-mTOR, and P-ERK1/2 and increased that of Ac-H3K9 and Ac-H4K8. In addition, using miRNA microarray and bioinformatics analysis, we detected that ACY-1215 promoted miR-30d expression, and PI3K regulatory subunit 2 (PIK3R2) was a direct target of miR-30d. Anti-miR-30d partially rescued the G2/M phase arrest and apoptosis caused by ACY-1215 treatment. The reductions in PI3K, P-AKT, and P-mTOR expression were also partially reversed by miR-30d inhibitor. Furthermore, the effects of ACY-1215 inhibited ESCC proliferation were validated in a mouse xenograft model in vivo. In conclusion, our study showed that ACY-1215 suppressed proliferation and promoted apoptosis in ESCC via miR-30d/PI3K/AKT/mTOR and ERK pathways and that ACY-1215 may be a promising antitumor agent in ESCC.

• Acute kidney injury
• Inflammatory injury
• JNK signaling pathway
• Lipopolysaccharide
• MicroRNA-30b
• NF-κB signaling pathway

• Lung cancer
• MicroRNAs
• Tumor markers

Systemic diffuse large B-cell lymphoma (DLBCL) is a potentially curable disease using current regimen of immunochemotherapy. Central nervous system (CNS) relapse is a complication that occurs in approximately 5% of DLBCL patients and is associated with a high fatality rate. Early identification of molecular markers for CNS involvement may serve for the highly needed accurate stratification of patients into risk groups regarding CNS relapse. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level and are known to be involved in DLBCL pathophysiology. In this study, we utilized miRNA multiplex reading of systemic newly diagnosed DLBCL samples obtained from patients with clinical risk factors for CNS involvement whose disease course was distinguished by the presence or absence of subsequent CNS relapse. The analysis detected two differentially expressed miRNAs, miR-20a and miR-30d, that predict for CNS involvement. Replication of these results in different samples was used for validation. We performed bioinformatics miRNA-target enrichment analysis to reveal a number of putative mechanisms for these miRNAs regulation of CNS relapse, including neuronal plasticity and WNT signaling pathway. Altogether, we show that the expression level of two miRNAs may have valuable information that may refine stratification for patients-at-risk for relapse with CNS involvement in DLBCL. Further larger scale studies are needed to shed light on the pathways involved in this disease.

• CNS relapse prediction
• miR-20a
• miR-30d
• microRNA
• systemic DLBCL

• Gerotarget
• chemo brain
• epigenetics
• microRNA
• tumor brain

• CNS (central nervous system)
• KHDRBS (KH domain RNA binding and signal transduction)
• RNA-binding proteins
• STAR (signal transduction and activation of RNA)
• alternative splicing
• neurexin

Cervical squamous cell carcinoma (CSCC) is the most frequent type among cervical cancers. Although the altered miRNA miR-30d expression and the amplified chromosome locus of MIR30D, 8q24, have been reported in somatic cancers, the definitive functional impact of such region especially in CSCC remains under-investigated.

One hundred thirty-six cases of CSCC tissues and matched adjacent normal ovarian epithelial tissues were assessed in this study. FISH and qPCR were performed to detect the copy number and microRNA expression of MIR30D gene in the collected samples. In in-vitro study, proliferation of CSCC cells were analyzed using WST-1 assay and invasion abilities of CSCC cells were evaluated by transwell assay. In-vivo study using a model of nude mice bearing tumor was also performed.

Copy number gains of MIR30D were detected in 22.8% (31 out of 136) of CSCC samples. Copy number of MIR30D was positively correlated with tumor progression. CSCCs with lymph node metastases (LNM) also showed more frequencies (36.4%) of MIR30D amplification than those without LNM (18.4%, p < 0.05). CSCCs with increased copy number of MIR30D also showed a positive correlation with miR-30d up-regulation. Inhibition of miR-30d in CSCC cells led to impaired tumor growth and migration.

Copy number amplifications of MIR30D gene and enhanced expression of miR-30d were positively correlated with tumor progression in CSCCs, indicating miR-30d might play an oncomiric role in the progression of CSCC.

The online version of this article (doi:10.1186/s12885-017-3201-0) contains supplementary material, which is available to authorized users.

• Cervical squamous cell carcinoma
• Copy number variation
• Gene expression
• MIR30D
• miR-30d

• MicroRNA-30d
• Myosin phosphatase targeting subunit 1
• Prognosis
• Prostate cancer
• Tumor angiogenesis

• Animals
• Biomarkers, Tumor
• Cell Line, Tumor
• Cell Movement/genetics
• Cell Proliferation
• Disease Models, Animal
• Disease Progression
• Gene Expression Profiling
• Gene Expression Regulation
• Heterografts
• Humans
• Male
• Mice
• MicroRNAs/genetics
• Myosin-Light-Chain Phosphatase/genetics
• Myosin-Light-Chain Phosphatase/metabolism
• Neovascularization, Pathologic/genetics
• Neovascularization, Pathologic/metabolism
• Prognosis
• Prostatic Neoplasms/genetics
• Prostatic Neoplasms/metabolism
• Prostatic Neoplasms/mortality
• Prostatic Neoplasms/pathology
• Proto-Oncogene Proteins c-jun/metabolism
• RNA Interference
• Signal Transduction
• Vascular Endothelial Growth Factor A/metabolism

• P01 CA120964 NCI NIH HHS

This study intends to investigate the correlations of miR-124a and miR-30d with clinicopathological features of breast cancer (BC) patients with type 2 diabetes mellitus (T2DM). A total of 72 BC patients with T2DM (diabetic group) and 144 BC patients without T2DM (non-diabetic group) were enrolled in this study. Blood glucose was detected by glucose oxidase methods. Glycosylated hemoglobin (HbA1c) was measured by high performance liquid chromatography. Fasting insulin (FIns) was measured by chemiluminescent microparticle immunoassay. Automatic biochemical analyzer was used to detect triglyceride, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Estradiol (E₂) was detected by radioimmunoassay. Homeostasis model assessment was applied to assess the insulin resistance (HOMA-IR) and β-cell insulin secretion (HOMA-IS). The expressions of miR124a and miR-30d were measured by quantitative real-time polymerase chain reaction (qRT-PCR). There were significant differences in age, the ratio of menopause, body mass index (BMI), HDL-C, TC, 2-h plasma glucose (2hPG), FIns, HbA1c, HOMA-IS and HOMA-IR between the diabetic and non-diabetic groups. The diabetic group had higher incidence of lymph node metastasis than non-diabetic group. The miR-124a expression was down-regulated while the miR-30d expression was up-regulated in BC patients with T2DM. The correlation analysis showed that miR-124a expression was positively correlated with HDL-C, while it was negatively correlated with age, HbA1c, LDL-C and E₂. However, the miR-30d expression was negatively correlated with HDL-C but positively correlated with age, HbA1c, LDL-C and E₂. In conclusion, miR-124a and miR-30d may be correlated with clinicopathological features of BC patients with T2DM. The miR-124a and miR-30d could serve as novel biomarkers for early diagnosis of BC in patients with T2DM.

• Breast cancer
• Clinicopathological features
• MicroRNA-124a
• MicroRNA-30d
• Type 2 diabetes mellitus

• 3,3′-Diindolylmethane
• ATG5
• Autophagy
• Gastric cancer
• miR-30e

• Autophagy
• Gastric cancer
• Gene expression
• Helicobacter pylori
• mir-30d

• 3' Untranslated Regions
• Autophagy/genetics
• Autophagy-Related Protein 12/genetics
• Autophagy-Related Protein 12/metabolism
• Autophagy-Related Protein 5/genetics
• Autophagy-Related Protein 5/metabolism
• Autophagy-Related Proteins/genetics
• Autophagy-Related Proteins/metabolism
• Beclin-1/genetics
• Beclin-1/metabolism
• Cell Line, Tumor
• Gastric Mucosa/metabolism
• Gastric Mucosa/microbiology
• Gastric Mucosa/ultrastructure
• Gene Expression Regulation, Neoplastic
• Helicobacter Infections/genetics
• Helicobacter Infections/metabolism
• Helicobacter Infections/microbiology
• Helicobacter pylori/metabolism
• Host-Pathogen Interactions
• Humans
• Membrane Proteins/genetics
• Membrane Proteins/metabolism
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Microbial Viability
• Proto-Oncogene Proteins/genetics
• Proto-Oncogene Proteins/metabolism
• Signal Transduction
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/microbiology
• Stomach Neoplasms/ultrastructure
• Time Factors
• Transfection
• Tumor Suppressor Proteins/genetics
• Tumor Suppressor Proteins/metabolism
• Up-Regulation
• Vesicular Transport Proteins/genetics
• Vesicular Transport Proteins/metabolism

• EIF5A2
• Gastric cancer
• Invasion
• Migration
• miR-30b

• 3' Untranslated Regions
• Antigens, CD
• Apoptosis
• Binding Sites
• Cadherins/genetics
• Cadherins/metabolism
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Computational Biology
• Databases, Genetic
• Epithelial-Mesenchymal Transition
• Gene Expression Regulation, Neoplastic
• Genes, Reporter
• HEK293 Cells
• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Neoplasm Invasiveness
• Peptide Initiation Factors/genetics
• Peptide Initiation Factors/metabolism
• RNA-Binding Proteins/genetics
• RNA-Binding Proteins/metabolism
• Signal Transduction
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/pathology
• Time Factors
• Transfection
• Vimentin/genetics
• Vimentin/metabolism
• Eukaryotic Translation Initiation Factor 5A

CNS tumours occur in both pediatric and adult patients and many of these tumours are associated with poor clinical outcome. Due to a paradigm shift in thinking for the last several years, these tumours are now considered to originate from a small population of stem-like cells within the bulk tumour tissue. These cells, termed as brain tumour initiating cells (BTICs), are perceived to be regulated by microRNAs at the posttranscriptional/translational levels. Proliferation, stemness, differentiation, invasion, angiogenesis, metastasis, apoptosis, and cell cycle constitute some of the significant processes modulated by microRNAs in cancer initiation and progression. Characterization and functional studies on oncogenic or tumour suppressive microRNAs are made possible because of developments in sequencing and microarray techniques. In the current review, we bring recent knowledge of the role of microRNAs in BTIC formation and therapy. Special attention is paid to two highly aggressive and well-characterized brain tumours: gliomas and medulloblastoma. As microRNA seems to be altered in the pathogenesis of many human diseases, “microRNA therapy” may now have potential to improve outcomes for brain tumour patients. In this rapidly evolving field, further understanding of miRNA biology and its contribution towards cancer can be mined for new therapeutic tools.

• CCNE2
• Motility
• Non-small cell lung cancer
• Proliferation
• miR-30d

MicroRNAs (miRNAs) are endogenous short non-coding RNAs that repress post-transcriptional regulation of gene expression, while embryonal central nervous system tumors are the foremost cause of mortality in children suffering from a neoplasm. MiRNAs and their regulatory mechanisms are new to understand, while pediatric CNS tumors are difficult to comprehend. Therefore, identification of the link between them composes a major scientific challenge. The present study, reviewed the current knowledge on the role of miRNA in pediatric CNS embryonal tumors, attempting to collect the existing information in one piece of work that could ideally be used as a guide for future reference and research.

Embryonal tumors of the central nervous system represent a heterogeneous group of childhood cancers with an unknown pathogenesis; diagnosis, on the basis of histological appearance alone, is controversial and patients’ response to therapy is difficult to predict. They encompass medulloblastoma, atypical teratoid/rhabdoid tumors and a group of primitive neuroectodermal tumors. All are aggressive tumors with the tendency to disseminate throughout the central nervous system. The large amount of genomic and molecular data generated over the last 5–10 years encourages optimism that new molecular targets will soon improve outcomes. Recent neurobiological studies have uncovered the key role of microRNAs (miRNAs) in embryonal tumors biology and their potential use as biomarkers is increasingly being recognized and investigated. However the successful use of microRNAs as reliable biomarkers for the detection and management of pediatric brain tumors represents a substantial challenge. This review debates the importance of miRNAs in the biology of central nervous systemembryonal tumors focusing on medulloblastoma and atypical teratoid/rhabdoid tumors and highlights the advantages as well as the limitations of their prospective application as biomarkers and candidates for molecular therapeutic targets.

• Animals
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use
• Biomarkers, Tumor/genetics
• Central Nervous System Diseases/drug therapy
• Central Nervous System Diseases/genetics
• Humans
• MicroRNAs/genetics
• Neoplasms, Germ Cell and Embryonal/drug therapy
• Neoplasms, Germ Cell and Embryonal/genetics

Gastric cancer is one of the most common malignant diseases worldwide. Emerging evidence has shown that microRNAs (miRNAs) are associated with tumor development and progression. Our previous studies have revealed that H. pylori infection was able to induce the altered expression of miR-30b in gastric epithelial cells. However, little is known about the potential role of miR-30b in gastric cancer.

We analyzed the expression of miR-30b in gastric cancer cell lines and human gastric cancer tissues. We examined the effect of miR-30b mimics on the apoptosis of gastric cancer cells in vitro by flow cytometry (FCM) and caspase-3/7 activity assays. Nude mouse xenograft model was used to determine whether miR-30b is involved in tumorigenesis of gastric cancer. The target of miR-30b was identified by bioinformatics analysis, luciferase assay and Western blot. Finally, we performed the correlation analysis between miR-30b and its target expression in gastric cancer.

miR-30b was significantly down-regulated in gastric cancer cells and human gastric cancer tissues. Enforced expression of miR-30b promoted the apoptosis of gastric cancer cells in vitro, and miR-30b could significantly inhibit tumorigenicity of gastric cancer by increasing the apoptosis proportion of cancer cells in vivo. Moreover, plasminogen activator inhibitor-1 (PAI-1) was identified as the potential target of miR-30b, and miR-30b level was inversely correlated with PAI-1 expression in gastric cancer. In addition, silencing of PAI-1 was able to phenocopy the effect of miR-30b overexpression on apoptosis regulation of cancer cells, and overexpression of PAI-1 could suppressed the effect of promoting cell apoptosis by miR-30b, indicating PAI-1 is potentially involved in miR-30b-induced apoptosis on cancer cells.

miR-30b may function as a novel tumor suppressor gene in gastric cancer by targeting PAI-1 and regulating the apoptosis of cancer cells. miR-30b could serve as a potential biomarker and therapeutic target against gastric cancer.

• Animals
• Apoptosis/genetics
• Biomarkers, Tumor/genetics
• Blotting, Western
• Carcinogenesis/genetics
• Cell Line, Tumor
• Cell Proliferation/genetics
• Down-Regulation
• Female
• Gene Expression Regulation, Neoplastic
• HEK293 Cells
• Humans
• Male
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs/genetics
• Middle Aged
• Plasminogen Activator Inhibitor 1/genetics
• Plasminogen Activator Inhibitor 1/metabolism
• Reverse Transcriptase Polymerase Chain Reaction
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/pathology
• Transplantation, Heterologous
• Tumor Burden/genetics

Embryonal tumors of the nervous system are the leading cause of childhood cancer-related morbidity and mortality. Medulloblastoma, supratentorial primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumor and neuroblastoma account for more than 20% of childhood malignancies and typify the current neural embryonal tumor model in pediatric oncology. Mechanisms driving the formation of these tumors point towards impaired differentiation of neuronal and neuron-associated cells during the development of the nervous system as an important factor. The importance of microRNAs (miRNAs) for proper embryonic cell function has been confirmed and their aberrant expressions have been linked to tumor development. The role of miRNAs in controlling essential regulators of key pathways implicated in tumor development makes their use in diagnostics a powerful tool to be used for early detection of cancer, risk assessment and prognosis, as well as for the design of innovative therapeutic strategies. In this review we focus on the significance of miRNAs involved in the biology of embryonal neural tumors, delineate their clinical significance and discuss their potential as a novel therapeutic target.

• BCL2
• KRAS
• PIK3CD
• apoptosis
• colorectal cancer
• miR-30b
• proliferation

Parkinson's Disease (PD) is a progressive neurologic disorder that affects movement and balance. Recent studies have revealed the importance of microRNA (miR) in PD. However, the detailed role of miR and its regulation by Transcription Factor (TF) remain unexplored. In this work for the first time we have studied TF-miR-mRNA regulatory network as well as miR co-expression network in PD.

We compared the 204 differentially expressed miRs from microarray data with 73 PD related miRs obtained from literature, Human MicroRNA Disease Database and found a significant overlap of 47 PD related miRs (p-value<0.05). Functional enrichment analyses of these 47 common (Group1) miRs and the remaining 157 (Group2) miRs revealed similar kinds of over-representative GO Biological Processes and KEGG pathways. This strengthens the possibility that some of the Group 2 miRs can have functional roles in PD progression, hitherto unidentified in any study. In order to explore the cross talk between TF, miR and target mRNA, regulatory networks were constructed. Study of these networks resulted in 14 Inter-Regulatory hub miRs whereas miR co-expression network revealed 18 co-expressed hub miRs. Of these 32 hub miRs, 23 miRs were previously unidentified with respect to their association with PD. Hierarchical clustering analysis further strengthens the roles of these novel miRs in different PD pathways. Furthermore hsa-miR-92a appeared as novel hub miR in both regulatory and co-expression network indicating its strong functional role in PD. High conservation patterns were observed for most of these 23 novel hub miRs across different species including human. Thus these 23 novel hub miRs can be considered as potential biomarkers for PD.

Our study identified 23 novel miR markers which can open up new avenues for future studies and shed lights on potential therapeutic targets for PD.

• Cluster Analysis
• Gene Expression Profiling
• Gene Expression Regulation
• Gene Regulatory Networks
• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Mitogen-Activated Protein Kinase Kinases/genetics
• Mitogen-Activated Protein Kinase Kinases/metabolism
• Parkinson Disease/genetics
• Parkinson Disease/pathology
• RNA, Messenger
• Transcription, Genetic

• cyclin E2
• microRNA-30d
• proliferation inhibition
• renal carcinoma cells
• renal cell carcinoma

• anoikis
• functional screens
• libraries
• miR-30b/c
• small RNAs

• 3' Untranslated Regions
• Anoikis/genetics
• Base Sequence
• Binding Sites
• Caspase 3/genetics
• Caspase 3/metabolism
• Cell Culture Techniques
• Cell Shape
• Enzyme Repression
• Female
• Gene Expression
• Gene Library
• HCT116 Cells
• HEK293 Cells
• Humans
• Mammary Glands, Human/cytology
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Morphogenesis
• RNA Interference

EF24 is a curcumin analog that has improved anticancer activity over curcumin, but its therapeutic potential and mechanism of action is unknown, which is important to address as curcumin targets multiple signaling pathways. EF24 inhibits the NF-κB but not the JAK-STAT signaling pathway in DU145 human prostate cancer cells and B16 murine melanoma cells. EF24 induces apoptosis in these cells apparently by inhibiting miR-21 expression, and also enhances the expression of several miR-21 target genes, PTEN and PDCD4. EF24 treatment significantly suppressed the growth of DU145 prostate cancer xenografts in immunocompromised mice and resulted in tumor regression. EF24 enhanced the expression of the miR-21 target PTEN in DU145 tumor tissue, but suppressed the expression of markers of proliferating cells (cyclin D1 and Ki67). In syngeneic mice injected with B16 cells, EF24 treatment inhibited the formation of lung metastasis, prolonged animal survival, inhibited miR-21 expression and increased the expression of miR-21 target genes. Expression profiling of miRNAs regulated by EF24 in vitro and in vivo showed that the antitumor activity of EF24 reflected the enhanced expression of potential tumor suppressor miRNAs as well as the suppressed expression of oncogenic miRNAs, including miR-21. Taken together, our data suggest that EF24 is a potent anticancer agent and selectively targets NF-κB signaling and miRNA expression, indicating that EF24 has significant potential as a therapeutic agent in various cancers.

• Animals
• Antineoplastic Agents/pharmacology
• Apoptosis
• Benzylidene Compounds/pharmacology
• Cell Line, Tumor
• Gene Expression/drug effects
• Gene Expression Regulation, Neoplastic/drug effects
• Humans
• Male
• Melanoma, Experimental/drug therapy
• Mice
• Mice, Inbred C57BL
• Mice, Inbred NOD
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Piperidones/pharmacology
• Prostatic Neoplasms/drug therapy
• RNA Interference
• Signal Transduction
• Transcription Factor RelA/metabolism
• Xenograft Model Antitumor Assays

• R01 CA133322 NCI NIH HHS
• CA133322 NCI NIH HHS