Prohibitin regulates mTOR pathway via interaction with FKBP8 / 医学前沿

The ability of tumor cells to sustain continuous proliferation is one of the major characteristics of cancer. The activation of oncogenes and the mutation or inactivation of tumor suppressor genes ensure the rapid proliferation of tumor cells. The PI3K-Akt-mTOR axis is one of the most frequently modified signaling pathways whose activation sustains cancer growth. Unsurprisingly, it is also one of the most commonly attempted targets for cancer therapy. FK506 binding protein 8 (FKBP8) is an intrinsic inhibitor of mTOR kinase that also exerts an anti-apoptotic function. We aimed to explain these contradictory aspects of FKBP8 in cancer by identifying a "switch" type regulator. We identified through immunoprecipitation-mass spectrometry-based proteomic analysis that the mitochondrial protein prohibitin 1 (PHB1) specifically interacts with FKBP8. Furthermore, the downregulation of PHB1 inhibited the proliferation of ovarian cancer cells and the mTOR signaling pathway, whereas the FKBP8 level in the mitochondria was substantially reduced. Moreover, concomitant with these changes, the interaction between FKBP8 and mTOR substantially increased in the absence of PHB1. Collectively, our finding highlights PHB1 as a potential regulator of FKBP8 because of its subcellular localization and mTOR regulating role.

Relationship between methylation of RSK4 gene and papillary thyroid carcinoma / 中华内分泌代谢杂志

Objective To detect the methylation status of ribosomal S6 kinase 4 ( RSK4 ) in papillary thyroid carcinoma ( PTC) and to study its correlation with mRNA expression and clinical features. Methods 134 cases PTC tissues and corresponding paracancerous thyroid tissues were collected. DNA methylation status of RSK4 gene in PTC tissues and corresponding paracancerous tissues were analyzed by methylation specific PCR and bisulfite genomic sequencing, and mRNA expression was detected by quantitative realtime PCR. The relationship of DNA methylation status with mRNA expression and clinical features was analyzed. Results The methylation rate of RSK4 in PTC tissues was significantly higher than that in paracancerous tissues by methylation specific PCR ( P<0.05) and bisulfite genomic sequencing ( P<0. 01 ) . The RSK4 mRNA level in PTC tissues was significantly lower than that in paracancerous tissues ( P<0.01) . In PTC tissues, RSK4 mRNA expression in methylation group was lower than that in unmethylation group ( P<0.01) . The RSK4 mRNA level in PTC of methylation was lower than that in paracancerous tissues of methylation ( P<0. 01);the RSK4 mRNA level in PTC of unmethylation was also lower than that in paracancerous tissues of unmethylated ones ( P<0. 01 ) . There was relationship of RSK4 hypermethylation with lymphatic metastasis and TNM grade ( P<0. 05 ) . Serum concentration, of thyroid stimulating hormone, thyroid peroxidase antibody, and thyroglobulin antibody in methylation group were higher than those in unmethylation group ( P<0.05) . Conclusion The hypermethylation of RSK4 promoter's CpG islands might be one of the mechanisms for poor expression of RSK4 in PTC, which may serve as a molecular target of early diagnosis and treatment.

Relationship between methylation of RSK4 gene and papillary thyroid carcinoma / 中华内分泌代谢杂志

Objective@#To detect the methylation status of ribosomal S6 kinase 4 (RSK4)in papillary thyroid carcinoma (PTC)and to study its correlation with mRNA expression and clinical features.@*Methods@#134 cases PTC tissues and corresponding paracancerous thyroid tissues were collected. DNA methylation status of RSK4 gene in PTC tissues and corresponding paracancerous tissues were analyzed by methylation specific PCR and bisulfite genomic sequencing, and mRNA expression was detected by quantitative realtime PCR. The relationship of DNA methylation status with mRNA expression and clinical features was analyzed.@*Results@#The methylation rate of RSK4 in PTC tissues was significantly higher than that in paracancerous tissues by methylation specific PCR (P<0.05)and bisulfite genomic sequencing (P<0.01). The RSK4 mRNA level in PTC tissues was significantly lower than that in paracancerous tissues (P<0.01). In PTC tissues, RSK4 mRNA expression in methylation group was lower than that in unmethylation group (P<0.01). The RSK4 mRNA level in PTC of methylation was lower than that in paracancerous tissues of methylation (P<0.01); the RSK4 mRNA level in PTC of unmethylation was also lower than that in paracancerous tissues of unmethylated ones (P<0.01). There was relationship of RSK4 hypermethylation with lymphatic metastasis and TNM grade (P<0.05). Serum concentrations of thyroid stimulating hormone, thyroid peroxidase antibody, and thyroglobulin antibody in methylation group were higher than those in unmethylation group (P<0.05).@*Conclusion@#The hypermethylation of RSK4 promoter′s CpG islands might be one of the mechanisms for poor expression of RSK4 in PTC, which may serve as a molecular target of early diagnosis and treatment.