Wnt/ß-catenin pathway transactivates microRNA-150 that promotes EMT of colorectal cancer cells by suppressing CREB signaling.

A hallmark of aberrant activation of the Wnt/ß-catenin signaling pathway has been observed in most colorectal cancers (CRC), but little is known about the role of non-coding RNAs regulated by this pathway. Here, we found that miR-150 was the most significantly upregulated microRNA responsive to elevated of Wnt/ß-catenin signaling activity in both HCT116 and HEK293T cells. Mechanistically, the ß-catenin/LEF1 complex binds to the conserved TCF/LEF1-binding element in the miR-150 promoter and thereby transactivates its expression. Enforced expression of miR-150 in HCT116 cell line transformed cells into a spindle shape with higher migration and invasion activity. miR-150 markedly suppressed the CREB signaling pathway by targeting its core transcription factors CREB1 and EP300. Knockdown of CREB1 or EP300 and knockout of CREB1 by CRISPR/Cas9 phenocopied the epithelial-mesenchymal transition (EMT) observed in HCT116 cells in response to miR-150 overexpression. In summary, our data indicate that miR-150 is a novel Wnt effector that may significantly enhance EMT of CRC cells by targeting the CREB signaling pathway.

Bacterial Diversity and Community Structure in the Pine Wood Nematode Bursaphelenchus xylophilus and B. mucronatus with Different Virulence by High-Throughput Sequencing of the 16S rDNA.

Bursaphelenchus xylophilus is the pathogen of pine wilt disease. Bursaphelenchus mucronatus is similar to B. xylophilus in morphology. Both species share a common niche, but they are quite different in pathogenicity. Presently, the role of bacteria in pine wilt disease development has been widely speculated. The diversity of bacteria associated with B. xylophilus and B. mucronatus with different virulence remains unclear. In this study, virulence of four B. xylophilus and four B. mucronatus strains were evaluated by inoculating Pinus thunbergii. High-throughput sequencing targeted 16S rDNA of different virulence nematode strains was carried out. The associated bacterial community structures of the eight strains were analyzed. The results showed that 634,051 high-quality sequences were obtained from the eight nematode strains. The number of OTUs of bacteria associated with B. mucronatus was generally greater than those of B. xylophilus. The richness of the community of bacteria associated with high virulent B. xylophilus ZL1 and AmA3 was higher than moderately virulent B. xylophilus AA3, HE2, and all B. mucronatus strains. While the diversity of bacteria associated with B. mucronatus was higher than B. xylophilus. Stenotrophomonas, Pseudomonadaceae_Unclassified or Rhizobiaceae_Unclassified were predominant in the nematode strains with different virulence. Oxalobacteraceae and Achromobacter were found more abundant in the low virulent B. xylophilus and non-virulent B. mucronatus strains.

FoxM1 Drives a Feed-Forward STAT3-Activation Signaling Loop That Promotes the Self-Renewal and Tumorigenicity of Glioblastoma Stem-like Cells.

The growth factor PDGF controls the development of glioblastoma (GBM), but its contribution to the function of GBM stem-like cells (GSC) has been little studied. Here, we report that the transcription factor FoxM1 promotes PDGFA-STAT3 signaling to drive GSC self-renewal and tumorigenicity. In GBM, we found a positive correlation between expression of FoxM1 and PDGF-A. In GSC and mouse neural stem cells, FoxM1 bound to the PDGF-A promoter to upregulate PDGF-A expression, acting to maintain the stem-like qualities of GSC in part through this mechanism. Analysis of the human cancer genomic database The Cancer Genome Atlas revealed that GBM expresses higher levels of STAT3, a PDGF-A effector signaling molecule, as compared with normal brain. FoxM1 regulated STAT3 transcription through interactions with the ß-catenin/TCF4 complex. FoxM1 deficiency inhibited PDGF-A and STAT3 expression in neural stem cells and GSC, abolishing their stem-like and tumorigenic properties. Further mechanistic investigations defined a FoxM1-PDGFA-STAT3 feed-forward pathway that was sufficient to confer stem-like properties to glioma cells. Collectively, our findings showed how FoxM1 activates expression of PDGF-A and STAT3 in a pathway required to maintain the self-renewal and tumorigenicity of glioma stem-like cells.

[A clinical analysis for sudden sensorineural hearing loss with acoustic neurinoma].

OBJECTIVE: Retrospectively analyzed the clinical data of sudden sensorineural hearing loss with acoustic neuroma. METHODS: The clinical data of 467 cases with sudden sensorineural hearing loss were collected between Jan, 2008 and Aug, 2012. Discussed the clinical data which were diagnosed as acoustic neuroma. RESULTS: In 467 cases of sudden sensorineural hearing loss, nine cases were diagnosed as acoustic neuromas (9 ears, 1.93%), two males and seven females, with a age range of 28 to 57 years. Among them, seven cases accompanied with tinnitus, seven cases with vertigo. The hearing results in nine cases, two cases were found to be mild, two were moderate, four were severe, and one was profound hearling loss respectively. Hearing was classified into five types according to audiogram shape (1 of up-sloping, 1 of down-sloping, 2 of mid-frequency, 1 of profound loss, 4 of flat audiogram). Eight cases had abnormal ABR, nine cases with ear ipsilateral stapedius reflex were completely not elicited, seven cases with health ear contralateral stapedius reflex were completely not elicited. Tumors were graded by Koos Grades according to size (7 of grade I, 1 of grade II, 1 of grade IV). Seven small acoustic neuroma was taken waiting strategies. Meanwhile, we use glucocorticoid and improve the microcirculation of the inner ear medication short-termly for these patients. Four patients' hearing were improved. CONCLUSIONS: The initial symptoms of some acoustic neuroma are sudden hearing loss, especially the small tumors in internal auditory canal. In order to prevent misdiagnosis, MRI and ABR should be performed as a routine test for sudden sensorineural hearing loss. It is necessary to give appropriate treatment to protecting hearing for the small acoustic neuroma patients whose first symptoms are diagnosed as sudden sensorineural hearing loss.

Isolation and identification of phytate-degrading rhizobacteria with activity of improving growth of poplar and Masson pine.

A number of soil microorganisms can convert insoluble forms of phosphorus (P) to an accessible form to increase plant yields. Phytate is such a large kind of insoluble organic phosphorus that plants cannot absorb directly in soil, so the objectives of this study were to isolate, screen phytate-degrading rhizobacteria (PDRB), and to select potential microbial inocula that could increase the P uptake by plants. In this study, a total of 24 soil samples were collected from natural habitats of eight poplar and pine planting areas from the eastern to southern China. 17 PDRB strains were preliminarily screened from the rhizosphere soil of poplars and pines by the visible decolorization in the phytate selective medium. The highest ratio of the total diameter (colony + halo zone) to the colony diameter of the isolates was JZ-GX1, 3.85. Afterward, 17 PDRB strains were further determined for their abilities to degrade sodium phytate based on the amount of liberated inorganic P in liquid phytate specific medium. The results showed that the phytase ability of the three highest PDRB strains: JZ-GX1, JZ-DZ1 and JZ-ZJ1 were up to 2.58, 2.36 and 2.24 U/mL, respectively, much better than most of the bacteria reported in previous studies. In the soil-plant experiment, compared to CK, the best three strains of PDRB all could significantly promote growth of poplar and Masson pine under container growing. The three efficient PDRB strains were identified as follow: JZ-GX1, Rahnella aquatilis, both JZ-DZ1 and JZ-ZJ1 being autofluorescent, Pseudomonas fluorescens, by 16S rDNA gene sequencing technology, Biolog Identification System and biological characterization. The present study suggests that the three screened PDRB strains would have great potential application as biological fertilizers in the future.

miR-125b, a target of CDX2, regulates cell differentiation through repression of the core binding factor in hematopoietic malignancies.

MicroRNA-125b (miR-125b), a small noncoding RNA molecule, has been found to be deregulated and functions as an oncogene in many cancers including hematopoietic malignancies. However, the mechanisms accounting for miR-125b dysregulation remain to be elucidated. The present study aims to identify the factors that might contribute to up-regulation of miR-125b in human hematopoietic malignancies and its downstream targets for lineage-specific differentiation. We at first reported that CDX2, a homeobox transcription factor, binds to promoter regions of the miR-125b gene and activates transcriptional regulation of miR-125b in malignant myeloid cells. We further revealed that increasing levels of CDX2 in malignant myeloid cells activate miR-125b expression, which in turn inhibits core binding factor ß (CBFß) translation, thereby counteracting myeloid cell differentiation, at least for granulocytic lineage, and promoting leukemogenesis. Interestingly, we found that this novel pathway including CDX2, miR-125b, and CBFß was mediated by undergoing all-trans-retinoic acid induction. Once differentiation ensues with all-trans-retinoic acid treatment, CDX2 activity decreases, leading to a reduction in miR-125b transcription and up-regulation of CBFß in myeloid cells and in patients. The study provides a new mechanism that contributes to hematopoietic malignancies, which could involve deregulation of miR-125b and its up- and downstream factors. As altered expression of miRNAs has been reported in a wide range of malignancies, delineating the underlying molecular mechanisms of aberrant miRNA expression and characterizing the upstream and downstream factors will help to understand important steps in the pathogenesis of these afflictions.

[Pathological features and clinical managements of nasopharyngeal angiofibroma].

OBJECTIVE: To study the pathological features of nasopharyngeal angiofibroma (NA) and the principles for clinical managements. METHODS: Thirty-five patients with NAs were treated in First Affiliated Hospital of Fujian Medical University from Oct. 1981 to May 2007. The pathological changes, sites of origin, causes of intraoperative bleeding and the experiences of managements were retrospectively analysed. Using Fish stage: 6 cases were in stage I, 8 cases were in stage II, 17 cases were in stage III, 4 cases were stage IV. Two cases via endoscopic surgery, 2 cases via palatal approach, 19 cases via midfacial degloving approach, 9 cases via lateral rhinotomy approach, 3 cases via craniofacial combined approach. RESULTS: In nasal cavity and paranasal sinus, the tumor was covered by squamous or columnar epithelium. The tumor extensions such as in pterygopalatine fossa and infratemporal fossa were covered by fibrous pseudocapsule. All cases of this series originated in the lateral wall of posterior portion of the nasal cavity. Fifteen of thirty-five cases confidentially originated near sphenopalatine foramen. Large and thick vessels in the pedicle region were the exact sites of serious intraoperative bleeding. Thirty-one cases were totally removed. Four cases were subtotal resected. Visual loss revealed in 6 cases, 4 cases visual acuity improved postoperatively. Three cases revealed postoperative dry eye due to surgical involvement of the sphenopalatine ganglion. CONCLUSIONS: nasopharyngeal angiofibroma is covered by epithelium or pseudo-capsule, it does not infiltrate the surrounding tissue. Dissecting along the surface of tumor might decrease bleeding and facilitate removal of tumor. An ideal surgical management should be done according to actually size and image examination, to the greatest extent keeping normal facial appearance. Attention should be paid to the complications such as visual loss and dry eye.

[Mitochondrial 12S rRNA gene A827G in two pedigrees with nonsyndromic deafness].

OBJECTIVE: To investigate the relationship of associating mitochondrial DNA 12S rRNA gene mutations with non-syndromic and aminoglycoside-induced hearing loss happening to Chinese families. METHODS: The diagnosis was validated by hearing tests. Blood samples were collected from 20 family members (13 subjects from pedigree A and 7 from pedigree B) and 32 sporadic deafness cases. DNA was extracted from the leukocytes in blood samples. The gene fragments of mitochondrial DNA 12S rRNA, tRNA(Ser(UCN)) and GJB(2) were amplified by polymerase chain reaction (PCR). PCR products were analyzed by sequencing. RESULTS: The target gene fragments of all individuals were successfully amplified by PCR. The mitochondrial DNA 12S rRNA 827 A to G transition was detected from all maternal members including 12 patients with hearing loss, which was the homoplasmic mutation. Non-maternal members in two pedigrees did not carry this mutation. However, the tRNA(Ser(UCN)) A7445G, 12SrRNA A1555G and GJB2 gene mutations were not found from both the family members of two pedigrees and sporadic patients. One sporadic individual (1/32) who was diagnosed as aminoglycoside-induced hearing impairment carried A827G mutation too. CONCLUSION: It is confirmed that the mitochondrial DNA 12S rRNA gene is a hot spot for mutations associated with non-syndromic inherited hearing loss. The 12S rRNA nt827 A to G mutation may play a pivotal role in the pathogenesis of hearing impairment in two Chinese pedigrees.

[Expression profile in the cell lines of human TNFAIP1 gene].

TNFAIP1 was first identified as a tumor necrosis factor alpha(TNFalpha) and interleukin-6 (IL-6) inducible protein. Experiments on human and rat suggested the protein may play roles in the DNA repair, DNA synthesis, cell apoptosis and human diseases. But its real function and mechanism have not been reported. In this paper, the expression of TNFAIP1 were determined in a number of cell lines by Real-time PCR. We found that the expression levels of TNFAIP1 are high in COS7 and NIH3T3 cell lines but low in the cancer cell lines. These suggest that TNFAIP1 may be involved in the process of cancer. The over-expression of human TNFAIP1 can accelerate the apoptosis of HeLa cell.