A multicomponent-based microemulsion for boosting ovarian cancer therapy through dual modification with transferrin and SA-RH.

Balancing the antitumor activity and systemic toxicity of tripterine still faces a big challenge due to the narrow therapeutic window. To address this issue, we report a microemulsion system based on tripterine, brucea oil, and glycyrrhizin, and dual modified with both transferrin and cell-penetrating peptide SA-RH (Tf/SA-RH-TBG-MEs) for combinational and tumor-targeted cancer therapy. Such a microemulsion exhibited a spherical shape with a size of ~50 nm and a mildly-negative charge.

Silenced PITX1 promotes chemotherapeutic resistance to 5-fluorocytosine and cisplatin in gastric cancer cells.

Resistance to chemotherapeutic drugs leads to a poor prognosis in gastric cancer (GC). The present study aimed to assess the association between pituitary homeobox paired homeodomain transcription 1 (PITX1) expression and the sensitivity of GC cells to the chemotherapeutic drugs 5-fluorouracil (5-FU) and cisplatin (CDDP). In the present study, the gastric cancer cell lines GES-1, AGS, BGC-823, MCG-803 and SGC-7901 were used.

H3K9me3, H3K36me3, and H4K20me3 Expression Correlates with Patient Outcome in Esophageal Squamous Cell Carcinoma as Epigenetic Markers.

Background: Histone methylation, as an essential pattern of posttranslational modifications, contributes to multiple cancer-related biological processes. Dysregulation of histone methylation is now considered a biomarker for cancer prognosis.

Aims: This study investigated and evaluated the potential role of four histone lysine trimethylation markers as biomarkers for esophageal squamous cell carcinoma (ESCC) prognosis.

Elevated TFAP4 regulates lncRNA TRERNA1 to promote cell migration and invasion in gastric cancer.

Cancer cell invasion and metastasis are the leading causes of the high mortality rates in patients with malignant tumors. There is accumulating evidence to indicate that dysregulated long non‑coding RNAs (lncRNAs) may be involved in the progression of tumor invasion and metastasis. However, the regulatory mechanisms of the aberrant expression of lncRNAs remain largely unknown, although the roles of lncRNAs as drivers of tumor suppressive and oncogenic functions have appeared in prevalent cancer types in recent years.

Downregulated PITX1 Modulated by MiR-19a-3p Promotes Cell Malignancy and Predicts a Poor Prognosis of Gastric Cancer by Affecting Transcriptionally Activated PDCD5.

Background/aims: PITX1 has been identified as a potential tumor-suppressor gene in several malignant tumors. The molecular mechanism underlying PITX1, particularly its function as a transcription factor regulating gene expression during tumorigenesis, is still poorly understood.

Methods: The expression level and location of PITX1 were determined by quantitative reverse transcription PCR (qRT-PCR) and immunohistochemical staining in gastric cancer (GC).

DNA methyltransferase 3A isoform b contributes to repressing E-cadherin through cooperation of DNA methylation and H3K27/H3K9 methylation in EMT-related metastasis of gastric cancer.

DNA methyltransferase 3A (DNMT3A) has been recognised as a key element of epigenetic regulation in normal development, and the aberrant regulation of DNMT3A is implicated in multiple types of cancers, especially haematological malignancies. However, its clinical significance and detailed functional role in solid tumours remain unknown, although abnormal expression has gained widespread attention in these cancers. Here, we show that DNMT3A isoform b (DNMT3Ab), a member of the DNMT3A isoform family, is critical for directing epithelial-mesenchymal transition (EMT)-associated metastasis in gastric cancer (GC).

HBx represses RIZ1 expression by DNA methyltransferase 1 involvement in decreased miR-152 in hepatocellular carcinoma.

Hepatitis B virus (HBV) is mainly suspected to promote hepatocellular carcinoma (HCC) development by epigenetic alteration. The HBV X protein (HBx) plays a key role in the molecular pathogenesis of HBV-related HCC. However, the mechanism of HBx-mediated hepatocarcinogenesis remains to be elucidated.

HBx-upregulated lncRNA UCA1 promotes cell growth and tumorigenesis by recruiting EZH2 and repressing p27Kip1/CDK2 signaling.

It is well accepted that HBx plays the major role in hepatocarcinogenesis associated with hepatitis B virus (HBV) infections. However, little was known about its role in regulating long noncoding RNAs (lncRNAs), a large group of transcripts regulating a variety of biological processes including carcinogenesis in mammalian cells. Here we report that HBx upregulates UCA1 genes and downregulates p27 genes in hepatic LO2 cells.

Genome-wide profiling of DNA methylation reveals preferred sequences of DNMTs in hepatocellular carcinoma cells.

Aberrant DNA methylation of CpG site is among the earliest and most frequent alterations in developmental process and diseases including cancer. To elucidate the functional preferred site of DNMTs, we analyzed the feature of distinct methylated sequences and established the defined relationship between DNMTs and preference genomic DNA sequences. Small interfering RNA (siRNA) construct of DNTM1, DNMT3A, and DNMT3B was transfected into the human hepatocellular carcinoma cell line SMMC-7721, respectively.

Reduced miR-29a-3p expression is linked to the cell proliferation and cell migration in gastric cancer.

Background: MicroRNAs (miRNAs) play an important role in a tumor-suppressive or oncogenic manner in carcinogenesis. Alteration expression patterns of miRNAs in gastric cancer (GC) are associated with cancer initiation and progression. In the present study, we evaluated miR-29a-3p expression pattern and its function in gastric carcinogenesis.

Deregulation between miR-29b/c and DNMT3A is associated with epigenetic silencing of the CDH1 gene, affecting cell migration and invasion in gastric cancer.

The de-regulation of the miR-29 family and DNA methyltransferase 3A (DNMT3A) is associated with gastric cancer (GC). While increasing evidence indicates miR-29b/c could regulate DNA methylation by targeting DNMT3A, it is currently unknown if epigenetic silencing of miR-29b/c via promoter hypermethylation in GC is caused by abnormal expression of DNMT3A. Thus, we aimed to evaluate whether cross-talk regulation exists between miR-29b/c and DNMT3A and whether it is associated with a malignant phenotype in GC.

Hypermethylation and clinicopathological significance of RASAL1 gene in gastric cancer.

Background: Recent studies have suggested that expression of the RAS protein activator like-1 gene (RASAL1) is decreased in gastric carcinoma tissues and cell lines, indicated a role in tumorigenesis and development of gastric cancer. Reduced expression of RASAL1 could result in aberrant increase of activity of RAS signaling pathways in cancer cells. However, the exact mechanism which induces down-regulation of the RASAL1 gene remains unclear.

Enforced expression of RASAL1 suppresses cell proliferation and the transformation ability of gastric cancer cells.

RAS protein activator like 1 (RASAL1) is a member of the RAS GTPase-activating protein (GAP) family, and it is an important molecule in the regulation of RAS activation. In the present study, we investigated the role of RASAL1 in gastric carcinogenesis. Decreased expression pattern of RASAL1 in gastric cancer tissues and cell lines was found in protein and RNA levels, although there was no statistically significant relationship between RASAL1 and clinicopathological features.

Association of the DNMT3A -448A>G polymorphism with genetic susceptibility to colorectal cancer.

The DNA methyltransferase 3A (DNMT3A) -448A>G polymorphism is a novel functional single nucleotide polymorphism (SNP) that contributes to the genetic susceptibility to gastric cancer. In this study, we aimed to assess the genotype frequencies of DNMT3A -448A>G in colorectal cancer (CRC) patients and healthy control subjects, and to explore the association of the DNMT3A functional SNP, -448A>G, with genetic susceptibility to CRC. Genomic DNA was extracted from samples of 258 patients with CRC and 280 healthy controls.

Depletion of DNMT3A suppressed cell proliferation and restored PTEN in hepatocellular carcinoma cell.

Promoter hypermethylation mediated by DNA methyltransferases (DNMTs) is the main reason for epigenetic inactivation of tumor suppressor genes (TSGs). Previous studies showed that DNMT1 and DNMT3B play an important role in CpG island methylation in tumorigenesis. Little is known about the role of DNMT3A in this process, especially in hepatocellular carcinoma (HCC).

Epigenetic activation of E-cadherin is a candidate therapeutic target in human hepatocellular carcinoma.

E-cadherin is a key cell adhesion molecule implicated in tumor suppression that is frequently altered in hepatocellular carcinoma (HCC), particularly in hepatitis B virus-related tumors. Here, we report that the epigenetic drugs 5-azacytidine and trichostatin A up-regulated E-cadherin expression in HCC cells. The depletion of DNMT1 restored E-cadherin expression via demethylation, whereas the depletion of DNMT3A or DNMT3B did not.

A functional polymorphism in the DNA methyltransferase-3A promoter modifies the susceptibility in gastric cancer but not in esophageal carcinoma.

Background: DNA-methyltransferase (DNMT)-3A plays an important role in the development of embryogenesis and the generation of aberrant methylation in carcinogenesis. The aim of this study was to investigate the role of a DNMT3A promoter genetic variant on its transcriptional activity and to evaluate the association between DNMT3A gene polymorphism and the susceptibility to gastric cancer (GC) and oesophagus carcinoma (EC) in the Chinese population.

Methods: We selected one of the single nucleotide polymorphisms (SNPs) -448A>G in the DNMT3A promoter region and evaluated its effect on activity using a luciferase assay.

Expression pattern and clinical significance of DNA methyltransferase 3B variants in gastric carcinoma.

The aim of this study was to detect the expression pattern of DNA methyltransferase 3B (DNMT3B) variants in primary gastric cancer (GC) and to explore the clinical significance of DNMT3B variants in gastric carcinogenesis. Specific polymerase chain reaction (PCR) primer sets were designed to distinguish individual DNMT3B variants according to their splicing patterns. Expression levels of DNMT3B variants were assessed by quantitative real-time RT-PCR in gastric cancer tissue, normal gastric mucosae and GC cell lines.

Overexpression of DNA methyltransferase 1 and its biological significance in primary hepatocellular carcinoma.

Aim: To explore the relationship between DNA methyltransferase 1 (DNMT1) and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) and its biological significance in primary HCC.

Methods: We carried out an immunohistochemical examination of DNMT1 in both HCC and paired non-neoplastic liver tissues from Chinese subjects. DNMT1 mRNA was further examined in HCC cell lines by real-time PCR.

Promoter polymorphisms of DNMT3B and the risk of colorectal cancer in Chinese: a case-control study.

Background: DNA-methyltransferase-3B (DNMT3B), which plays a role in DNA methylation, is usually aberrant expression involved in carcinogenesis. Polymorphisms of the DNMT3B gene may influence DNMT3B activity on DNA methylation in several cancers, thereby modulating the susceptibility to cancer.

Methods: DNMT3B -579G>T genotypes and -149C>T were determined by PCR-RFLP and sequencing in 137 colorectal cancer patients and 308 controls matched for age and sex, who did not receive radiotherapy or chemotherapy for newly diagnosed and histopathologically confirmed colorectal cancer.

DNMT3B 579 G>T promoter polymorphism and risk of esophagus carcinoma in Chinese.

Aim: To investigate the relationship between 579 G>T polymorphisms in the DNMT3B gene, which is involved in de novo methylation and associated with the risk of esophagus cancer (EC) in Chinese.

Methods: DNMT3B 579 G>T genotypes were determined by PCR-RFLP in 194 EC patients and 210 healthy controls matched for age and sex, who did not receive radiotherapy or chemotherapy for newly diagnosed and histopathologically confirmed EC.

Results: In control subjects, the frequency of T/T and G/T genotypes, and T and G alleles was 81.

DNA methyltransferase 1 knockdown induces silenced CDH1 gene reexpression by demethylation of methylated CpG in hepatocellular carcinoma cell line SMMC-7721.

Background: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality in the world; however, the molecular mechanisms leading to hepatocyte transformation, especially in epigenetic mechanisms (such as DNA methylation) are still poorly understood. DNA methyltransferase 1 (DNMT1) is the predominant maintenance methyltransferase gene required to maintain DNA methylation patterns in mammalian cells.

Aim And Methods: To explore the role of DNMT1 in the regulation of expression of tumor-related genes in human HCC cells via DNA methylation of the regulatory CpG islands, we stably transfected expression constructs containing small interfering RNA (siRNA) of DNMT1 into the human HCC cell line, SMMC-7721.

Identification of potential genes regulated by DNA methyltransferase 3B in a hepatocellular carcinoma cell line by RNA interference and microarray analysis.

Whether DNA methyltransferase 3B (DNMT3B) is deregulated in hepatocellular carcinoma cell lines is still unclear. The expression levels of DNMT3B protein in normal liver cell line, pericacinoma cell line and hepatocellular carcinoma cell lines were compared by both Western blotting and immunocytochemistry. Long-term downregulated DNMT3B in a hepatocellular carcinoma cell line SMMC-7721 was achieved using a RNAi recombinant plasmid.

[Construction of DNMT1 siRNA stable expressing vector and evaluation of its silenced efficiency in blocking gene expression].

Objective: To construct the specific stable expression and high efficiency small interfering RNA(siRNA) expression vector that can block DNMT1 gene function.

Methods: Using vector-based RNA interference technique, the authors constructed a vector to transcribe functional short interfering RNA (RNAi). After transfection by lipofectmine (TM) reagent, the treated cells were selected by G418.