The RNA polymerase II subunit B (RPB2) functions as a growth regulator in human glioblastoma.

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor with a poor prognosis. The growth of GBM cells depends on the core transcriptional apparatus, thus rendering RNA polymerase (RNA pol) complex as a candidate therapeutic target. The RNA pol II subunit B (POLR2B) gene encodes the second largest subunit of the RNA pol II (RPB2); however, its genomic status and function in GBM remain unclear.

The BRD4 Inhibitor dBET57 Exerts Anticancer Effects by Targeting Superenhancer-Related Genes in Neuroblastoma.

Neuroblastoma (NB) is the most common solid tumor of the neural crest cell origin in children and has a poor prognosis in high-risk patients. The oncogene MYCN was found to be amplified at extremely high levels in approximately 20% of neuroblastoma cases. In recent years, research on the targeted hydrolysis of BRD4 to indirectly inhibit the transcription of the MYCN created by proteolysis targeting chimaera (PROTAC) technology has become very popular.

Super-enhancer profiling identifies novel critical and targetable cancer survival gene LYL1 in pediatric acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) is a myeloid neoplasm makes up 7.6% of hematopoietic malignancies. Super-enhancers (SEs) represent a special group of enhancers, which have been reported in multiple cell types.

BRD4 inhibitor GNE987 exerts anti-cancer effects by targeting super-enhancers in neuroblastoma.

Background: Neuroblastoma (NB) is a common extracranial malignancy with high mortality in children. Recently, super-enhancers (SEs) have been reported to play a critical role in the tumorigenesis and development of NB via regulating a wide range of oncogenes Thus, the synthesis and identification of chemical inhibitors specifically targeting SEs are of great urgency for the clinical therapy of NB. This study aimed to characterize the activity of the SEs inhibitor GNE987, which targets BRD4, in NB.

SAPCD2 promotes neuroblastoma progression by altering the subcellular distribution of E2F7.

Recent studies uncovered the emerging roles of SAPCD2 (suppressor anaphase-promoting complex domain containing 2) in several types of human cancer. However, the functions and underlying mechanisms of SAPCD2 in the progression of neuroblastoma (NB) remain elusive. Herein, through integrative analysis of public datasets and regulatory network of GSK-J4, a small-molecule drug with anti-NB activity, we identified SAPCD2 as an appealing target with a high connection to poor prognosis in NB.

CEBPG promotes acute myeloid leukemia progression by enhancing EIF4EBP1.

Background: Acute myeloid leukemia (AML) is a myeloid neoplasm accounts for 7.6% of hematopoietic malignancies. AML is a complex disease, and understanding its pathophysiology is contributing to the improvement in the treatment and prognosis of AML.

MI-773, a breaker of the MDM2/p53 axis, exhibits anticancer effects in neuroblastoma via downregulation of INSM1.

Neuroblastoma (NB) is a common pediatric malignancy associated with poor outcomes. Recent studies have shown that murine double minute2 homolog (MDM2) protein inhibitors are promising anticancer agents. MI-773 is a novel and specific antagonist of MDM2, however, the molecular mechanism of its anti-NB activity remains unclear.

mRNA expression profiling of histone modifying enzymes in pediatric acute monoblastic leukemia.

Histone modification is dysregulated in various types of cancers, including hematological malignancies. However, the expression profile of histone-modifying enzymes in pediatric acute monoblastic leukemia (AML FAB M5) has not been investigated. In this study, we evaluated the mRNA expression profile of 85 genes that encode enzymes involved in histone-modification in 27 pediatric AML FAB M5 samples by using a novel real-time PCR array.

Molecular mechanism of G arrest and cellular senescence induced by LEE011, a novel CDK4/CDK6 inhibitor, in leukemia cells.

Background: Overexpression of cyclin D1 dependent kinases 4 and 6 (CDK4/6) is a common feature of many human cancers including leukemia. LEE011 is a novel inhibitor of both CDK4 and 6. To date, the molecular function of LEE011 in leukemia remains unclear.

Inhibiting PLK1 induces autophagy of acute myeloid leukemia cells via mammalian target of rapamycin pathway dephosphorylation.

Decreased autophagy is accompanied by the development of a myeloproliferative state or acute myeloid leukemia (AML). AML cells are often sensitive to autophagy‑inducing stimuli, prompting the idea that targeting autophagy can be useful in AML cytotoxic therapy. AML NB4 cells overexpressing microtubule-associated protein 1 light chain 3-green fluorescent protein were screened with 69 inhibitors to analyze autophagy activity.

A novel sphingosine kinase 1 inhibitor (SKI-5C) induces cell death of Wilms' tumor cells and .

Sphingosine kinase 1 (SphK1) is over-expressed in many cancers and therefore serves as a biomarker for cancer prognosis. SKI-5C is a new SphK1 inhibitor, and until now its molecular function in Wilms' tumor cells remained unknown. Here, using CCK-8 and nude mice experiments we assessed cell growth in Wilms' tumor cell lines (SK-NEP-1 and G401) and .

Microarray profiling of bone marrow long non-coding RNA expression in Chinese pediatric acute myeloid leukemia patients.

Long non-coding RNA (lncRNA) plays a role in gene transcription, protein expression and epigenetic regulation; and altered expression results in cancer development. Acute myeloid leukemia (AML) is rare in children; and thus, this study profiled lncRNA expression in bone marrow samples from pediatric AML patients. Arraystar Human LncRNA Array V3.

Hypermethylation of the GATA binding protein 4 (GATA4) promoter in Chinese pediatric acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) is the second-most common form of leukemia in children. Aberrant DNA methylation patterns are a characteristic feature of AML. GATA4 has been suggested to be a tumor suppressor gene regulated by promoter hypermethylation in various types of human cancers although the expression and promoter methylation of GATA4 in pediatric AML is still unclear.

Molecular Mechanism of the Cell Death Induced by the Histone Deacetylase Pan Inhibitor LBH589 (Panobinostat) in Wilms Tumor Cells.

Background: Wilms tumor (WT) is an embryonic kidney cancer, for which histone acetylation might be a therapeutic target. LBH589, a novel targeted agent, suppresses histone deacetylases in many tumors. This study investigated the antitumor activity of LBH589 in SK-NEP-1 and G401 cells.

Analyzing the gene expression profile of anaplastic histology Wilms' tumor with real-time polymerase chain reaction arrays.

Background: Wilms' tumor (WT) is one of the most common malignant neoplasms of the urinary tract in children. Anaplastic histology (unfavorable histology) accounts for about 10% of whole WTs, and it is the single most important histologic predictor of treatment response and survival in patients with WT; however, until now the molecular basis of this phenotype is not very clearly.

Methods: A real-time polymerase chain reaction (PCR) array was designed and tested.

tp53-dependent G2 arrest mediator candidate gene, Reprimo, is down-regulated by promoter hypermethylation in pediatric acute myeloid leukemia.

Reprimo (RPRM) is a novel tumor suppressor. However, the expression and molecular function of RPRM in pediatric acute myeloid leukemia (AML) is still unknown. We observed hypermethylation of the RPRM promoter in 8/11 leukemia cell lines and in 44.

Early B-cell factor 3 (EBF3) is a novel tumor suppressor gene with promoter hypermethylation in pediatric acute myeloid leukemia.

Background: Pediatric acute myeloid leukemia (AML) comprises up to 20% of all childhood leukemia. Recent research shows that aberrant DNA methylation patterning may play a role in leukemogenesis. The epigenetic silencing of the EBF3 locus is very frequent in glioblastoma.

Molecular targeting of the oncoprotein PLK1 in pediatric acute myeloid leukemia: RO3280, a novel PLK1 inhibitor, induces apoptosis in leukemia cells.

Polo-like kinase 1 (PLK1) is highly expressed in many cancers and therefore a biomarker of transformation and potential target for the development of cancer-specific small molecule drugs. RO3280 was recently identified as a novel PLK1 inhibitor; however its therapeutic effects in leukemia treatment are still unknown. We found that the PLK1 protein was highly expressed in leukemia cell lines as well as 73.

Histone acetyltransferase inhibitor II induces apoptosis in glioma cell lines via the p53 signaling pathway.

Background: Histone acetyltransferase (HAT) inhibitors can inhibit proliferation and induce apoptosis in cancer cell lines. The novel cell-permeable p300/CREB-binding protein (CBP)-selective HAT inhibitor HATi II can reduce histone H3 acetylation and induce chromatin condensation in HeLa cells. Here, we examined the effects and mechanism of action of HATi II in glioma cell lines.

Zinc finger protein 382 is downregulated by promoter hypermethylation in pediatric acute myeloid leukemia patients.

Acute myeloid leukemia (AML) is the second-most common form of leukemia in children. Aberrant DNA methylation patterns are characteristic of AML. Zinc finger protein 382 (ZNF382) has been suggested to be a tumor suppressor gene possibly regulated by promoter hypermethylation in various types of human cancer.

Metallothionein III (MT3) is a putative tumor suppressor gene that is frequently inactivated in pediatric acute myeloid leukemia by promoter hypermethylation.

Background: Acute myeloid leukemia (AML) is the second most common form of leukemia in children. Aberrant DNA methylation patterns are a characteristic feature in various tumors, including AML. Metallothionein III (MT3) is a tumor suppresser reported to show promoter hypermethylated in various cancers.

The promoter of miR-663 is hypermethylated in Chinese pediatric acute myeloid leukemia (AML).

Background: There is growing evidence supporting a role for microRNAs (miRNA) as targets in aberrant mechanisms of DNA hypermethylation. Epigenetic silencing of tumor suppressor miRNAs, including miR-663, which has recently been reported to be inactivated by hypermethylation in several cancers, may play important roles in pediatric acute myeloid leukemia (AML). However, expression of miR-663 and its promoter methylation remain status unclear in childhood leukemia.

Differential mRNA expression levels of human histone-modifying enzymes in normal karyotype B cell pediatric acute lymphoblastic leukemia.

Histone modification enzymes regulate gene expression by altering the accessibility of promoters to transcription factors. We sought to determine whether the genes encoding histone modification enzymes are dysregulated in pediatric acute lymphoblastic leukemia (ALL). A real-time PCR array was designed, tested and used to profile the expression of 85 genes encoding histone modification enzymes in bone marrow mononuclear cells from 30 pediatric ALL patients and 20 normal controls.

Survivin selective inhibitor YM155 induce apoptosis in SK-NEP-1 Wilms tumor cells.

Background: Survivin, a member of the family of inhibitor of apoptosis proteins, functions as a key regulator of mitosis and programmed cell death. YM155, a novel molecular targeted agent, suppresses survivin, which is overexpressed in many tumor types. The aim of this study was to determine the antitumor activity of YM155 in SK-NEP-1 cells.