RNF31 represses cell progression and immune evasion via YAP/PD-L1 suppression in triple negative breast Cancer.

BACKGROUND: Recently genome-based studies revealed that the abnormality of Hippo signaling is pervasive in TNBC and played important role in cancer progression. RING finger protein 31 (RNF31) comes to RING family E3 ubiquitin ligase. Our previously published studies have revealed RNF31 is elevated in ER positive breast cancer via activating estrogen signaling and suppressing P53 pathway. METHODS: We used several TNBC cell lines and xenograft models and performed immuno-blots, QPCR, in vivo studies to investigate the function of RNF31 in TNBC progression. RESULT: Here, we demonstrate that RNF31 plays tumor suppressive function in triple negative breast cancer (TNBC). RNF31 depletion increased TNBC cell proliferation and migration in vitro and in vitro. RNF31 depletion in TNBC coupled with global genomic expression profiling indicated Hippo signaling could be the potential target for RNF31 to exert its function. Further data showed that RNF31 depletion could increase the level of YAP protein, and Hippo signaling target genes expression in several TNBC cell lines, while clinical data illustrated that RNF31 expression correlated with longer relapse-free survival in TNBC patients and reversely correlated with YAP protein level. The molecular biology assays implicated that RNF31 could associate with YAP protein, facilitate YAP poly-ubiquitination and degradation at YAP K76 sites. Interestingly, RNF31 could also repress PDL1 expression and sensitive TNBC immunotherapy via inhibiting Hippo/YAP/PDL1 axis. CONCLUSIONS: Our study revealed the multi-faced function of RNF31 in different subtypes of breast malignancies, while activation RNF31 could be a plausible strategy for TNBC therapeutics.

UHRF1 modulates breast cancer cell growth via estrogen signaling.

The ubiquitination process, which involves that binding of an ubiquitin protein to certain substrates, regulates several human biological processes and human cancers. Several studies report that the abnormal expression of quite a few E3 ubiquitin ligases could play critical role in carcinogenic process and cancer progression. In our current study, we identify UHRF1 (Ubiquitin Like with PHD And Ring Finger Domain 1) is an important regulator for breast cancer growth. UHRF1 depletion significantly decreases breast cancer growth in vitro and in vivo. Clinical data analysis reveals that UHRF1 is dramatically elevated in breast cancer, compared to normal breast tissue. UHRF1 correlates with poor survival in luminal type of breast cancer patients, but not in ER-negative groups. The molecular biological studies show that UHRF1 localizes in the nuclear and interact with ERα via its SRA domain, which subsequently inhibits K48-linked ubiquitination of ERα and enhances ERα stability. Our study provides a novel function of UHRF1 in regulation estrogen signaling in breast cancer and a promising target for breast cancer therapeutics.

Assessing the microbial community and functional genes in a vertical soil profile with long-term arsenic contamination.

Arsenic (As) contamination in soil and groundwater has become a serious problem to public health. To examine how microbial communities and functional genes respond to long-term arsenic contamination in vertical soil profile, soil samples were collected from the surface to the depth of 4 m (with an interval of 1 m) after 16-year arsenic downward infiltration. Integrating BioLog and functional gene microarray (GeoChip 3.0) technologies, we showed that microbial metabolic potential and diversity substantially decreased, and community structure was markedly distinct along the depth. Variations in microbial community functional genes, including genes responsible for As resistance, carbon and nitrogen cycling, phosphorus utilization and cytochrome c oxidases were detected. In particular, changes in community structures and activities were correlated with the biogeochemical features along the vertical soil profile when using the rbcL and nifH genes as biomarkers, evident for a gradual transition from aerobic to anaerobic lifestyles. The C/N showed marginally significant correlations with arsenic resistance (p = 0.069) and carbon cycling genes (p = 0.073), and significant correlation with nitrogen fixation genes (p = 0.024). The combination of C/N, NO(3) (-) and P showed the highest correlation (r = 0.779, p = 0.062) with the microbial community structure. Contradict to our hypotheses, a long-term arsenic downward infiltration was not the primary factor, while the spatial isolation and nutrient availability were the key forces in shaping the community structure. This study provides new insights about the heterogeneity of microbial community metabolic potential and future biodiversity preservation for arsenic bioremediation management.

Skermanella stibiiresistens sp. nov., a highly antimony-resistant bacterium isolated from coal-mining soil, and emended description of the genus Skermanella.

A Gram-negative, aerobic, motile, rod-shaped, antimony-resistant bacterium, designated strain SB22(T), was isolated from soil of Jixi coal mine, China. The major cellular fatty acids (>5 %) were C(18:1)ω7c (63.5 %), summed feature 2 (C(14:0) 3-OH and/or iso-C(16:1) I, 10.8 %) and C(16:0) (9.9 %). The major polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and an unknown aminolipid. The genomic DNA G+C content was 69.6 mol% and Q-10 was the major respiratory quinone. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain SB22(T) was most closely related to Skermanella aerolata 5416T-32(T) (97.3 %), Skermanella parooensis ACM 2042(T) (95.8 %) and Skermanella xinjiangensis 10-1-101(T) (92.9 %). The DNA-DNA hybridization value between strain SB22(T) and S. aerolata KACC 11604(T) ( = 5416T-32(T)) was 43.3 %. On the basis of phenotypic, chemotaxonomic and phylogenetic characteristics of strain SB22(T) and related species, it is considered that the isolate represents a novel species of the genus Skermanella, for which the name Skermanella stibiiresistens sp. nov. is proposed. The type strain is SB22(T) ( = CGMCC 1.10751(T) = KCTC 23364(T)). An emended description of the genus Skermanella is provided.

Cellulomonas carbonis sp. nov., isolated from coal mine soil.

A Gram-positive, aerobic, motile, rod-shaped bacterium, designated strain T26(T), was isolated from subsurface soil of Tianjin coal mine, China. Colonies were yellow-white, convex, circular, smooth and non-transparent on R2A agar. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain T26(T) was closely related to members of the genus Cellulomonas and a member of the genus Actinotalea with 96.8-94.7% and 96.7% gene sequence similarities, respectively. The peptidoglycan type of strain T26(T) was A4ß, containing l-ornithine-d-glutamic acid as the interpeptide bridge. The cell-wall sugars were rhamnose, galactose, xylose and inositol. The major fatty acids (>10%) were anteiso-C(15:0) (33.6%), anteiso-C(15:1) A (22.1%), C(16:0) (14.4%) and C(14:0) (12.1%). The predominant respiratory quinone was MK-9(H(4)) and the genomic DNA G+C content was 74.4 mol%. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol-mannosides and phosphatidylinositol. Comparison of phenotypic and phylogenetic characteristics between strain T26(T) and related organisms revealed that the new isolate represented a novel species of the genus Cellulomonas, for which the name Cellulomonas carbonis sp. nov. is proposed. The type strain is T26(T) ( = CGMCC 1.10786(T) = KCTC 19824(T) = CCTCC AB2010450(T)).

Lysobacter arseniciresistens sp. nov., an arsenite-resistant bacterium isolated from iron-mined soil.

A Gram-negative, aerobic, motile, rod-shaped, arsenite [As(III)]-resistant bacterium, designated strain ZS79(T), was isolated from subsurface soil of an iron mine in China. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain ZS79(T) clustered closely with strains of five Lysobacter species, with 96.9, 96.1, 96.0, 95.8 and 95.3% sequence similarities to Lysobacter concretionis Ko07(T), L. daejeonensis GH1-9(T), L. defluvii IMMIB APB-9(T), L. spongiicola KMM 329(T) and L. ruishenii CTN-1(T), respectively. The major cellular fatty acids were iso-C(15:0) (28.6%), iso-C(17:1)ω9c (19.9%), iso-C(16:0) (13.6%), iso-C(11:0) (12.6%) and iso-C(11:0) 3-OH (12.4%). The genomic DNA G+C content was 70.7 mol% and the major respiratory quinone was Q-8. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and an unknown phospholipid. On the basis of morphological and physiological/biochemical characteristics, phylogenetic position and chemotaxonomic data, this strain is considered to represent a novel species of the genus Lysobacter, for which the name Lysobacter arseniciresistens sp. nov. is proposed; the type strain is ZS79(T) (=CGMCC 1.10752(T)=KCTC 23365(T)).

An ent-kaurane diterpenoid from Isodon japonica var. glaucocalyx.

The title compound, 14ß-acet-oxy-7α-hydr-oxy-ent-kaur-16-ene-3,15-dione or glaucocalyxin B, C(22)H(30)O(5), a natural ent-kaurane diterpenoid, is composed of four rings with the expected cis and trans ring junctions. In the crystal structure, there are two mol-ecules in the asymmetric unit related by a noncrystallographic twofold screw axis, and ring A is disordered [ratio occupancies 0.829 (19):0.171 (19)], such that both chair and boat conformations are present, but with the boat conformation as the major component. In the crystal, mol-ecules are linked by inter-molecular O-H⋯O hydrogen bonds.

[Cloning and identification of fibrinogen gamma polypeptide (FGG) gene differentially expressed in human hepatocellular carcinoma].

BACKGROUND & OBJECTIVE: Abnormal expression of genes is related to development and progression of hepatocellular carcinoma (HCC); however, the detailed mechanism is unclear yet because the known genetic information is not sufficient at present. This study was to explore cloning and identification of fibrinogen gamma polypeptide (FGG) gene differentially expressed in human hepatocellular carcinoma. METHODS: The suppression subtractive hybridization was used to obtain subtracted cDNA products of HCC, then the products were cloned by T/A method. The differential expression of gene in HCC was identified by DNA sequencing analysis, Northern blot analysis, rapid amplification of cDNA end (RACE), and reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Firstly, a cDNA fragment of 787 nucleotides was screened from the subtracted cDNA clones, and it was further discovered that the expression of the cDNA fragment was higher significantly in human hepatocellular carcinoma cell strains of SMMC-7721 and HepG2 than in normal hepatocytes by Northern blot analysis. The RACE was carried out and the gene of 1 597 bp containing polyA in 3'end was obtained, which has an entire open reading frame encoding 437 amino acids. Homology analysis showed that this was a gene encoding human FGG. RT-PCR analysis of FGG showed that the amplification of cancerous tissues, especially in metastasis of HCC, was raised as compared to that of adjacent non-cancerous tissues. CONCLUSION: Overexpression of FGG was discovered in SMMC-7721 and HepG2 cells. The up-regulation of FGG may be associated with the pathogenesis of HCC.