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Three novel ovine genes were obtained from muscle full-length cDNA library of black-boned sheep. Sequence analysis revealed that nucleotide sequences of these genes were not homologous to any of the known sheep or goat genes, but these genes have high similarity to ATP synthase subunit O (ATP5O), NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 12 (NDUFA12) and ubiquinol-cytochrome c reductase hinge protein (UQCRH) genes of other mammal animals (accession number: FJ546085, FJ546078 and FJ546083). The alignment analysis showed that the ovine ATP5O, NDUFA12 and UQCRH genes and proteins have closer genetic relationships with the ATP5O, NDUFA12 and UQCRH genes and proteins from cattle. Conserved domain prediction showed that these three genes included OSCP, NDUFA12 superfamily and UCR-hinge superfamily domains respectively. The deduced sequence of ATP5O, NDUFA12 and UQCRH protein had 213, 145 and 91 amino acid residues, with a molecular weight of approximately 23419.66, 17089.50 and 10657.75 Da and a theoretical isoelectric point of 9.90, 9.68 and 4.45. The secondary structure prediction revealed that 60% helix structure in ATP5O, 60% coils in NDUFA12 and no strand in UQCRH. One potential signal peptide structure in ATP5O protein were found. NDUFA12 and UQCRH have the extremely low possibility of signal peptides. Meanwhile, RasMol was used for visualizing the PDB files generated by Swiss-Model in cartoon or three-dimensional format. ATP5O and UQCRH protein were modeled by Swiss-Model. Tissue expression profile indicated that the ovine ATP5O, NDUFA12 and UQCRH genes could be expressed in all detected tissues including muscles, heart, liver, spleen, lung, kidney and adipose tissues, but the expression abundance of these genes were various in the different tissues. Our experiment supplied the primary foundation for further researches on these three ovine genes. [ABSTRACT FROM AUTHOR]

Abstract: The analysis of a small number of patients with atypical chronic myeloid leukemia showing balanced chromosomal translocations has revealed diverse tyrosine kinase fusion genes, most commonly involving FGFR1, PDGFRA, PDGFRB, JAK2, and ABL. We present a case of aCML with a 3q22;21q22-translocation that led to truncation of the receptor-like tyrosine kinase (RYK) gene and its juxtaposition with sequences from chromosome 21 including the ATP5O gene coding for a mitochondrial ATP synthase. The resulting fusion was not in frame, however, which is why we speculate that an abrogated RYK gene product rather than a chimeric protein might be the leukemogenic result. [Copyright &y& Elsevier]

Simple Summary: Due to the heterogeneity of prostate cancer (PCa), it is still difficult to provide risk stratification. Metabolic changes in PCa tissue have been described during tumor progression at genetic and transcriptomic level, but these have not yet clearly contributed to improved diagnosis and therapy. The aim of our study was to identify novel markers for aggressive prostate cancer in a proteomics-derived dataset by immunohistochemical analysis and correlation with transcriptomic data. Here, we provide potential new markers—NDUFS1 and ATP5O—for risk stratification in PCa. Additionally, we reveal for the first time a concordant increase of NDUFS1/ATP5O of mRNA expression in transcriptomic datasets and at protein level. We aimed to identify novel markers for aggressive prostate cancer in a STAT3-low proteomics-derived dataset of mitochondrial proteins by immunohistochemical analysis and correlation with transcriptomic data and biochemical recurrence in a STAT3 independent PCa cohort. Formalin-fixed paraffin-embedded tissue (FFPE) sample selection for proteomic analysis and tissue-microarray (TMA) generation was conducted from a cohort of PCa patients. Retrospective data analysis was performed with the same cohort. 153 proteins differentially expressed between STAT3-low and STAT3-high samples were identified. Out of these, 46 proteins were associated with mitochondrial processes including oxidative phosphorylation (OXPHOS), and 45 proteins were upregulated, including NDUFS1/ATP5O. In a STAT3 independent PCa cohort, high expression of NDUFS1/ATP5O was confirmed by immunocytochemistry (IHC) and was significantly associated with earlier biochemical recurrence (BCR). mRNA expression levels for these two genes were significantly higher in intra-epithelial neoplasia and in PCa compared to benign prostate glands. NDUFS1/ATP5O levels are increased both at the mRNA and protein level in aggressive PCa. Our results provide evidence that NDUFS1/ATP5O could be used to identify high-risk PCa patients. [ABSTRACT FROM AUTHOR]

Our previous study has proved that down-regulation of CLDN10 (Claudin-10) in ccRCC (clear cell renal cell carcinoma) was closely related to tumor metastasis and predicted an unfavorable prognosis by analyzing TCGA-KIRC data. However, the effects of CLDN10 on the progression of ccRCC and its mechanisms of action remain elusive. During the study, a large number of clinical samples were utilized to verify the reduced expression of CLDN10 in ccRCC and its association with tumor metastasis and poor prognosis, and our results confirmed that lower CLDN10 expression was an independent predictor of shorter OS (HR: 4.0860, 95%CI: 2.4737-6.7490, P<0.0001) and DFS (HR: 4.3680, 95%CI: 2.2800-8.3700, P<0.0001) in metastatic ccRCC patients. CLDN10 overexpression accelerated cell apoptosis and restrained cell proliferation, migration and invasion in vitro . Besides, CLDN10 overexpression suppressed ccRCC growth and lung metastasis and promoted apoptosis in orthotopic models. Mechanistically, we found that CLDN10 overexpression up-regulated the acetylation and expression levels of ATP5O (ATP synthase subunit O, mitochondrial), leading to the dysfunction of mitochondrial, thereby suppressing the growth and metastasis of ccRCC through increasing the levels of NDUFS2, ROS, Cleaved-Caspase 3, E-cadherin and SDHB and decreasing the levels of N-cadherin and mitochondrial membrane potential. Moreover, knockdown of ATP5O expression based on the overexpression of CLDN10 could reverse the increase in NDUFS2, ROS, Cleaved-Caspase 3, E-cadherin and SDHB levels, the decrease in N-cadherin and mitochondrial membrane potential levels and the inhibition of ccRCC phenotypes caused by CLDN10 overexpression. Taken together, these findings for the first time illuminate the mechanism by which CLDN10 overexpression suppresses the growth and metastasis of ccRCC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Aim: To explore the effect of lysine acetylation in related proteins on regulation of the proliferation of gastric cancer cells, and determine the lysine-acetylated proteins and the acetylated modified sites in AGS gastric cancer cells., Methods: The CCK-8 experiment and flow cytometry were used to observe the changes in proliferation and cycle of AGS cells treated with trichostatin A (TSA). Real time polymerase chain reaction and Western blotting were used to observe expression changes in p21, p53, Bax, Bcl-2, CDK2, and CyclinD1 in gastric cancer cells exposed to TSA. Cytoplasmic proteins in gastric cancer cells before and after TSA treatment were immunoprecipitated with anti-acetylated lysine antibodies, separated using sodium dodecyl sulfate polyacrylamide gel electrophoresis gel and silver-stained to detect the proteins by mass spectrometry after removal of the gel. The acetylated proteins in AGS cells were enriched with lysine-acetylated antibodies, and a high-resolution mass spectrometer was used to detect the acetylated proteins and modified sites., Results: TSA significantly inhibited AGS cell proliferation, and promoted cell apoptosis, leading to AGS cell cycle arrest in G0/G1 and G2/M phases, especially G0/G1 phase. p21, p53 and Bax gene expression levels in AGS cells were increased with TSA treatment duration; Bcl-2, CDK2, and CyclinD1 gene expression levels were decreased with TSA treatment duration. Two unknown protein bands, 72 kDa (before exposure to TSA) and 28 kDa (after exposure to TSA), were identified by silver-staining after immunoprecipitation of AGS cells with the lysine-acetylated monoclonal antibodies. Mass spectrometry showed that the 72 kDa protein band may be PKM2 and the 28 kDa protein band may be ATP5O. The acetylated proteins and modified sites in AGS cells were determined., Conclusion: TSA can inhibit gastric cancer cell proliferation, which possibly activated signaling pathways in a variety of tumor-associated factors. ATP5O was obviously acetylated in AGS cells following TSA treatment.