The Association between Genetic Polymorphism and the Processing Efficiency of miR-149 Affects the Prognosis of Patients with Head and Neck Squamous Cell Carcinoma

MicroRNAs (miRNAs) play important roles in modulating the neoplastic process of cancers including head and neck squamous cell carcinoma (HNSCC). A genetic polymorphism (rs2292832, C>T) has been recently identified in the precursor of miR-149; nevertheless its clinicopathological implications remain obscure. In this study, we showed that miR-149 is down-regulated in HNSCC compared to normal mucosa and this is associated with a poorer patient survival. In addition, HNSCC patients with the T/T genotype have more advanced tumors and a worse prognosis. Multivariate analysis indicated that patients carried the T/T genotype have a 2.81-fold (95% CI: 1.58–4.97) increased risk of nodal metastasis and 1.66-fold (95% CI: 1.05–2.60) increased risk of mortality compared to other groups. T/T genotype also predicted the worse prognosis of buccal mucosa carcinoma subset of HNSCC. In vitro analysis indicated that exogenous miR-149 expression reduces the migration of HNSCC cells. Moreover, HNSCC cell subclones carrying the pri-mir-149 sequence containing the T variant show a low processing efficacy when converting the pre-mir-149 to mature miR-149. These findings suggest that miR-149 suppresses tumor cell mobility, and that the pre-mir-149 polymorphism may affect the processing of miR-149, resulting in a change in the abundance of the mature form miRNA, which, in turn, modulates tumor progression and patient survival.     

Seasonal dynamics of soil fauna in the subalpine and alpine forests of west Sichuan at different altitudes

The climate (especially temperature) often plays an important role in the structure, function as well as composition of soil organisms in different latitudes and altitudes. As one of the essential components of soil ecosystem, soil faunal community not only lays their roles as soil engineer in material cycling and energy flow, but also acts as the sensitive bio-indicator to environmental change. However, little information has been available on the responses of soil faunal community to the changed environment at different altitudes and seasons. In order to understand the seasonal dynamics of soil faunal diversity under different forests with varying altitudes, three fir (Abies faxoniana) forests were selected covering a 600 m vertical transition zone. The primary fir forest at 3600 m (A1) of altitude, mixed fir and birch forest at 3300 m (A2) of altitude, and secondary fir forest at 3000 m (A3) of altitude are representative forests in the subalpine and alpine region of west Sichuan. A 2 years study was conducted in the three subalpine and alpine forests from May in 2009 until October in 2010. Soil samples were collected in both the soil organic layer and mineral soil layer. Soil macro-fauna were picked up by hand in the fields. Meso/micro-fauna and damp living fauna were separated and collected from the soil samples by Baermann and Tullgren methods in laboratory, respectively. A total of 74,827 individuals were collected in the 2 years, belonging to seven phyla, 16 classes, 31 orders and 125 families by preliminary identification. Similar dominant groups were detected in different forests at different altitudes, consisting of Spirostreptida, Formicidae, Staphylinidae, Hesperinidae, Onychiuridae, Isotomidae, Oribatuloidae, Alicoragiidae, Secernentea, and Adenophorea. In contrast, the ordinary species of macro-fauna and the ratios of Acarina to Collembolan were obviously different. For instance, the ordinary species were dominated by Cydmaenidae and Mycetophilidae at the A1, Scaphidiidae and Helicinidae at the A2, and Lumbricida and Agelenidae at the A3, respectively. Both the individual density and the number of soil faunal groups were significantly higher in soil organic layer than those in mineral soil layer. The density and group of macro-, meso- and micro-fauna in different forests showed the order as A2 > A1 > A3, but the density of damp living fauna showed the order as A1 > A2 > A3. The functional groups of macro-fauna were mainly dominated by saprozoic. The highest density and group of macro-fauna was observed in August, while the highest value of meso/micro-fauna was detected in October. In addition, the Jacard similarity indices showed that the composition and structure of soil fauna were similar in the different forests varied with altitudes, but the Shannon–Wiener indices were significantly different. The highest values of Shannon–Wiener indices were observed in October at both the A1 and A3, and in August at the A2. The results suggested that soil faunal community kept a high diversity in the subalpine and alpine forests of west Sichuan, and their structures were significantly affected by the variation of altitudes, which provided important scientific evidences for understanding the ecological processes in the subalpine and alpine coniferous forests.     

Hyperosmolarity enhanced susceptibility to renal tubular fibrosis by modulating catabolism of type I transforming growth factor‐β receptors

Hyperosmolarity plays an essential role in the pathogenesis of diabetic tubular fibrosis. However, the mechanism of the involvement of hyperosmolarity remains unclear. In this study, mannitol was used to evaluate the effects of hyperosmolarity on a renal distal tubule cell line (MDCK). We investigated transforming growth factor‐β receptors and their downstream fibrogenic signal proteins. We show that hyperosmolarity significantly enhances the susceptibility to exogenous transforming growth factor (TGF)‐β1, as mannitol (27.5 mM) significantly enhanced the TGF‐β1‐induced increase in fibronectin levels compared with control experiments (5.5 mM). Specifically, hyperosmolarity induced tyrosine phosphorylation on TGF‐β RII at 336 residues in a time (0–24 h) and dose (5.5–38.5 mM) dependent manner. In addition, hyperosmolarity increased the level of TGF‐β RI in a dose‐ and time‐course dependent manner. These observations may be closely related to decreased catabolism of TGF‐β RI. Hyperosmolarity significantly downregulated the expression of an inhibitory Smad (Smad7), decreased the level of Smurf 1, and reduced ubiquitination of TGF‐β RI. In addition, through the use of cycloheximide and the proteasome inhibitor MG132, we showed that hyperosmolarity significantly increased the half‐life and inhibited the protein level of TGF‐β RI by polyubiquitination and proteasomal degradation. Taken together, our data suggest that hyperosmolarity enhances cellular susceptibility to renal tubular fibrosis by activating the Smad7 pathway and increasing the stability of type I TGF‐β receptors by retarding proteasomal degradation of TGF‐β RI. This study clarifies the mechanism underlying hyperosmotic‐induced renal fibrosis in renal distal tubule cells. J. Cell. Biochem. 109: 663–671, 2010. © 2010 Wiley‐Liss, Inc.     

沉没湖底的"华北之花"

提起新中国的第一个机械化农场——冀衡农场，也许很少有人知道。这个农场就淹没在衡水湖底……[编者按]     

Effect of Genetic Variants in Two Chemokine Decoy Receptor Genes,DARC and CCBP2, on Metastatic Potential of Breast Cancer

The inhibitory effect of two chemokine decoy receptors (CDRs), DARC and D6, on breast cancer metastasis is mainly due to their ability to sequester pro-malignant chemokines. We hypothesized that genetic variants in the DARC and CCBP2 (encoding D6) genes may be associated with breast cancer progression. In the present study, we evaluated the genetic contributions of DARC and CCBP2 to metastatic potential, indicated by lymph node metastasis (LNM). Ten single-nucleotide polymorphisms (SNPs) (potentially functional SNPs and block-based tagging SNPs) in DARC and CCBP2 were genotyped in 785 breast cancer patients who had negative lymph nodes and 678 patients with positive lymph nodes. Two non-synonymous SNPs, rs12075 (G42D) in DARC and rs2228468 (S373Y) in CCBP2, were observed to be associated with LNM in univariate analysis and remained significant after adjustment for conventional clinical risk factors, with odds ratios (ORs) of 0.54 (95% confidence interval [CI], 0.37 to 0.79) and 0.78 (95% CI, 0.62 to 0.98), respectively. Additional functional experiments revealed that both of these significant SNPs could affect metastasis of breast cancer in xenograft models by differentially altering the chemokine sequestration ability of their corresponding proteins. Furthermore, heterozygous GD genotype of G42D on human erythrocytes had a significantly stronger chemokine sequestration ability than homozygous GG of G42D ex vivo. Our data suggest that the genetic variants in the CDR genes are probably associated with the varied metastatic potential of breast cancer. The underlying mechanism, though it needs to be further investigated, may be that CDR variants could affect the chemokine sequestration ability of CDR proteins.