N6-methyladenosine-modified microRNA-675 advances the development of gastrointestinal stromal tumors via inhibiting myosin phosphatase targeting protein 1.

RNA N6-methyladenosine (m6A) modifications influence gastrointestinal stromal tumors (GISTs) development, but the detailed molecular mechanisms have not been fully studied. Here, microRNA-675 was found to be aberrantly elevated in cancerous tissues and cells of GISTs, compared to the corresponding normal counterparts, and GISTs patients with high-expressed microRNA-675 have worse outcomes. Additional experiments confirmed that silencing of microRNA-675 hindered cell division, mobility and tumorigenesis in vitro and in vivo, whereas triggered apoptotic cell death in GISTs cells. Furthermore, microRNA-675-ablation increased the expression levels of myosin phosphatase targeting protein 1 (MYPT1) to inactivate the tumor-initiating RhoA/NF2/YAP1 signal pathway, and downregulation of MYPT1 recovered the malignant phenotypes in microRNA-675-silenced GISTs cells. In addition, we evidenced that METTL3-mediated m6A modifications were essential for sustaining the stability of microRNA-675, and silencing of METTL3 restrained tumorigenesis of GISTs cells by regulating the microRNA-675/MYPT1 axis. To summarize, theMETTL3/m6A/microRNA-675/MYPT1 axis could be used as novel biomarkers for the diagnosis and treatment of GISTs.

Application of SNPs with low minor allele frequencies in missing person identification (MPI) through kinship analysis of DNA mixtures.

The need to identify a missing person (MP) through kinship analysis of DNA samples found at a crime scene has become increasingly prevalent. DNA samples from MPs can be severely degraded, contain little DNA and mixed with other contributors, which often makes it difficult to apply conventional methods in practice. This study developed a massively parallel sequencing-based panel that contains 1661 single-nucleotide polymorphisms (SNPs) with low minor allele frequencies (MAFs) (averaged at 0.0613) in the Chinese Han population, and the strategy for relationship inference from DNA mixtures comprising different numbers of contributors (NOCs) and of varying allele dropout probabilities. Based on the simulated dataset and genotyping results of 42 artificial DNA mixtures (NOC = 2-4), it was observed that the present SNP panel was sufficient for balanced mixtures when referenced to the closest relatives (parents/offspring and full siblings). When the mixture profiles suffered from dropout, incorrect assignments were markedly associated with relatedness, NOC and the dropout level. We, therefore, indicate that SNPs with low MAFs could be reliably interpreted for MP identification through the kinship analysis of complex DNA mixtures. Further studies should be extended to more possible scenarios to test the feasibility of this present approach.

MicroRNA-101 inhibits proliferation of pulmonary microvascular endothelial cells in a rat model of hepatopulmonary syndrome by targeting the JAK2/STAT3 signaling pathway.

Hepatopulmonary syndrome (HPS) is one of the reasons for the mortality of patients with perioperative liver disease. Intrapulmonary vascular dilatation is the most important mechanism underlying HPS, and it primarily occurs due to cell proliferation. Inhibiting the proliferation of pulmonary microvascular endothelial cells (PMVECs) may provide a novel strategy to prevent HPS. MicroRNAs (miRNAs) regulate gene expression and are crucial in cell proliferation. To investigate the mechanism underlying the proliferation of PMVECs in HPS, PMVECs were isolated from rat models of HPS. It was demonstrated that interleukin (IL)­6 could stimulate the janus kinase 2 (JAK2)/ signal transducer and activator of transcription (STAT3) signaling pathway, which promotes the cell proliferation of PMVECs. JAK2 is a novel target gene of miR-101 and it was shown that miR-101 could inhibit cell proliferation by targeting the IL-6/JAK2/STAT3 signal pathway. In conclusion, the present study demonstrated that miR-101 could inhibit the proliferation of PMVECs by targeting the IL-6/JAK2/STAT3 signaling pathway. This clarifies the role of miR-101 in HPS and provides the theoretical basis of the pathogenesis of HPS.

A network biology approach to discover the molecular biomarker associated with hepatocellular carcinoma.

In recent years, high throughput technologies such as microarray platform have provided a new avenue for hepatocellular carcinoma (HCC) investigation. Traditionally, gene sets enrichment analysis of survival related genes is commonly used to reveal the underlying functional mechanisms. However, this approach usually produces too many candidate genes and cannot discover detailed signaling transduction cascades, which greatly limits their clinical application such as biomarker development. In this study, we have proposed a network biology approach to discover novel biomarkers from multidimensional omics data. This approach effectively combines clinical survival data with topological characteristics of human protein interaction networks and patients expression profiling data. It can produce novel network based biomarkers together with biological understanding of molecular mechanism. We have analyzed eighty HCC expression profiling arrays and identified that extracellular matrix and programmed cell death are the main themes related to HCC progression. Compared with traditional enrichment analysis, this approach can provide concrete and testable hypothesis on functional mechanism. Furthermore, the identified subnetworks can potentially be used as suitable targets for therapeutic intervention in HCC.

Treatment of inflammatory bowel disease with Chinese drugs administered by both oral intake and retention enema.

OBJECTIVE: To study the clinical effect of Chinese drugs administered by both oral intake and retention enema on inflammatory bowel diseases (IBD). METHODS: Adopting a randomized controlled design, 78 patients were assigned to three groups: 26 patients in group A treated with Chinese drugs given by both oral intake and retention enema, 27 in group B with Chinese drugs given by retention enema only, and 25 in group C with given Western medicine. The changes before and after a 30-day treatment of the patients' symptoms (including diarrhea, abdominal pain, mucous or pus-bloody stool), colonoscopic examination scores and histopathology of the colonic membrane were observed. RESULTS: Group A showed the best outcomes in all the aspects of clinical comprehensive effectiveness. Improvements in the main symptoms, colonoscopic scores and histopathology of the colonic membrane were significantly different from those in groups B and C, respectively (P<0.05). Meanwhile comparisons between groups B and C showed insignificant differences (P>0.05); group B was better in ameliorating tenesmus (P<0.05). CONCLUSION: Through the use of Chinese drugs administered by both oral intake and retention enema to treat IBD, which combined external-internal therapies for both overall regulation and local management, it was confirmed that the Chinese medicine could embody the therapeutic principle of attending to both disease-diagnosis and syndrome-differentiation.