Downregulation of NEBL promotes migration and invasion of clear cell renal cell carcinoma by inducing epithelial-mesenchymal transition.

As a member of the nebulin protein family and a structural protein of cytoskeleton, NEBL plays an important role in cardiac diseases. Recently, literature have reported the involvement of NEBL in the occurrence and development of various cancers except clear cell renal cell carcinoma (ccRCC). In this study, we found that mRNA and protein of NEBL are downregulated remarkably in ccRCC tissues based on both the TCGA database and clinical samples we collected. The areas under curve values of NEBL analyzed based on the TCGA database, qRT-PCR and IHC results were 0.9376, 0.9733 and 0.9807, respectively. The lower mRNA level of NEBL was associated with worse outcomes in ccRCC patients. When overexpressing NEBL in ccRCC cell lines, the proliferation, migration and invasion of ccRCC cells were suppressed significantly, suggesting a tumor suppressor role of NEBL. In addition, we identified that NEBL is closely related to epithelial-mesenchymal transition (EMT), thereby reducing the motility of ccRCC cells. Furthermore, the lower expression of NEBL was correlated with ccRCC patients with distant organ metastasis. In summary, we firstly described the aberrant expression of NEBL and revealed its tumor suppressor role in ccRCC. Our data support that NEBL could serve as a valuable diagnostic and prognostic biomarker in ccRCC, as well as a promising therapeutic target.

Loss of ACOX1 in clear cell renal cell carcinoma and its correlation with clinical features.

Clear cell renal cell carcinoma (ccRCC) is a major pathological type of kidney cancer with a poor prognosis due to a lack of biomarkers for early diagnosis and prognosis prediction of ccRCC. In this study, we investigated the aberrant expression of Acyl-coenzyme A oxidase 1 (ACOX1) in ccRCC and evaluated its potential in diagnosis and prognosis. ACOX1 is the first rate-limiting enzyme in the peroxidation ß-oxidation pathway and is involved in the regulation of fatty acid oxidative catabolism. The mRNA and protein levels of ACOX1 were significantly downregulated in ccRCC, and its downregulation was closely associated with the tumor-node-metastasis stage of patients. The ROC curves showed that ACOX1 possesses a high diagnostic value for ccRCC. The OS analysis suggested that lower expression of ACOX1 was closely related to the worse outcome of patients. In addition, gene set enrichment analysis suggested that expression of ACOX1 was positively correlated with CDH1, CDH2, CDKL2, and EPCAM, while negatively correlated with MMP9 and VIM, which strongly indicated that ACOX1 may inhibit the invasion and migration of ccRCC by reversing epithelial-mesenchymal transition. Furthermore, we screened out that miR-16-5p is upregulated at the mRNA transcript level in ccRCC and negatively correlated with ACOX1. In conclusion, our results showed that ACOX1 is abnormally low expressed in ccRCC, suggesting that it could serve as a diagnostic and prognostic biomarker for ccRCC. Overexpression of miR-16-5p may be responsible for the inactivation of ACOX1.

Psychromonas profunda sp. nov., a psychropiezophilic bacterium from deep Atlantic sediments.

A psychropiezophilic bacterium, strain 2825T (=LMG 21260T =JCM 11437T), isolated from deep Atlantic sediments at a depth of 2770 m and a temperature of 2 degrees C, was found by polyphasic analysis to represent a novel species of the genus Psychromonas, Psychromonas profunda sp. nov. It is a strict psychrophile and a moderate piezophile, whose degree of piezophily is increased markedly when the temperature is raised to 10 degrees C. The piezophily of P. profunda is intermediate between that of the type species, Psychromonas antarctica, which is not piezophilic, and that of Psychromonas kaikoae, which is an obligate piezophile.

Moritella profunda sp. nov. and Moritella abyssi sp. nov., two psychropiezophilic organisms isolated from deep Atlantic sediments.

Strains 2674T (=LMG 21259T =JCM 11435T) and 2693T (=LMG 21258T =JCM 11436T) were isolated from Atlantic sediments at a temperature of 2 degrees C and a depth of 2815 m off the West African coast. Polyphasic evidence indicates that the two strains belong to the genus Moritella and represent distinct species, for which the names Moritella profunda sp. nov. (for strain 2674T) and Moritella abyssi sp. nov. (for strain 2693T) are proposed. The moderate piezophily of the two organisms is intermediate between that of the type species, Moritella marina, which is not piezophilic, and Moritella yayanosii, an obligate piezophile. Both are strict psychrophiles with slightly different cardinal temperatures: at 0.1 MPa, maximal growth rates are observed at 2 degrees C (M. profunda) and 4 degrees C (M. abyssi) with maximum temperatures of 12 degrees C (M. profunda) or 14 degrees C (M. abyssi). The optimal pressure is lower than that at the site of isolation, and raising the temperature to 10 degrees C makes the organisms more piezophilic.

Aspartate carbamoyltransferase from a psychrophilic deep-sea bacterium, Vibrio strain 2693: properties of the enzyme, genetic organization and synthesis in Escherichia coli.

The aspartate carbamoyltransferase (ATCase) genes of psychrophilic Vibrio strain 2693 were cloned by complementation in Escherichia coli and the enzyme was partly characterized. The genes constitute a pyrBI operon homologous to the cognate structure in E. coli where pyrB and pyrI respectively encode the catalytic and the regulatory chains of ATCase. The strong sequence similarities noted between Vibrio and E. coli ATCases include extensive conservation of residues involved in interactions between subunits, suggesting that the two enzymes have very similar tertiary and quaternary structures. Vibrio ATCase is, however, not activated by ATP and not synergistically inhibited by CTP and UTP. It is also much more thermolabile than E. coli ATCase. With respect to Pyrococcus abyssi and E. coli ATCases, Vibrio ATCase presents marked differences in composition which could be related to its psychrophilic character. The results of these structural and functional comparisons indicate that Vibrio 2693 ATCase is a suitable model for biochemical studies on structure-function relationships in a 'cold' allosteric enzyme. The operon is expressed from a promoter which is immediately followed by a pyrimidine-rich leader ORF terminating within a putative transcription attenuator. These genetic and enzymic data strengthen the evolutionary relationship already noted between Vibrionaceae and Enterobacteriaceae.