استكشف المجموعة الواسعة من العناوين المتاحة.

While organ‐confined prostate cancer (PCa) is mostly therapeutically manageable, metastatic progression of PCa remains an unmet clinical challenge. Resistance to anoikis, a form of cell death initiated by cell detachment from the surrounding extracellular matrix, is one of the cellular processes critical for PCa progression towards aggressive disease. Therefore, further understanding of anoikis regulation in PCa might provide therapeutic opportunities. Here, we discover that PCa tumours with concomitant inhibition of two tumour suppressor phosphatases, PP2A and PTEN, are particularly aggressive, having < 50% 5‐year secondary‐therapy‐free patient survival. Functionally, overexpression of PME‐1, a methylesterase for the catalytic PP2A‐C subunit, inhibits anoikis in PTEN‐deficient PCa cells. In vivo, PME‐1 inhibition increased apoptosis in in ovo PCa tumour xenografts, and attenuated PCa cell survival in zebrafish circulation. Molecularly, PME‐1‐deficient PC3 cells display increased trimethylation at lysines 9 and 27 of histone H3 (H3K9me3 and H3K27me3), a phenotype known to correlate with increased apoptosis sensitivity. In summary, our results demonstrate that PME‐1 supports anoikis resistance in PTEN‐deficient PCa cells. Clinically, these results identify PME‐1 as a candidate biomarker for a subset of particularly aggressive PTEN‐deficient PCa. A subset of prostate cancer (PCa) tumours present simultaneous inactivation of two tumour suppressor phosphatases; phosphatase and tensin homolog (PTEN) and protein phosphatase 2A (PP2A). PP2A is inhibited via overexpression of PME‐1. Such cancers are particularly aggressive and often relapse from standard therapy, indicating PME‐1 as a potential clinically applicable biomarker for PCa. Mechanistically, PME‐1 expression protects cancer cells from anoikis, promoting their survival outside the primary tumour.

Background Pancreatic cancer (PC) is a malignancy worldwide. Circular RNAs (circRNAs) affects the growth of PC, nonetheless the mechanism is blurry. Here, we reconnoitered the parts of hsa_circ_0050102 in PC. Methods Hsa_circ_0050102, microRNA‐218‐5p (miR‐218‐5p) and protein phosphatase methylesterase 1 (PPME1) abundances were indicated by quantitative RT‐PCR or Western blot. Moreover, the cell functions were uncovered. Additionally, the relation of miR‐218‐5p and hsa_circ_0050102 or PPME1 was identified by dual‐luciferase reporter assay. Ultimately, the mice teats were utilized to quantity the part of hsa_circ_0050102. Results Hsa_circ_0050102 and PPME1 contents were increased, and the miR‐218‐5p was dwindled in PC. Hsa_circ_0050102 lack subdued cell vitality, colony formation, cell migration and invasion, and angiogenesis, but endorsed cell apoptosis in PC cells. Furthermore, miR‐218‐5p was established to block the development of PC cells via PPME1. Hsa_circ_0050102 bound to miR‐218‐5p to adjust the content of PPME1. Conclusion Hsa_circ_0050102 expedited the expansion of PC through growing PPME1 abundance by adjusting miR‐218‐5p. Circ_0050102 promoted proliferation, migration and invasion, and angiogenesis, while repressed cell apoptosis of PC cells via miR‐218‐5p/PPME1 axis.

Background Most well‐differentiated thyroid carcinomas display good therapeutic outcomes, but there are still some patients who are not sensitive to the general treatments lose their treatment opportunities. Thus, it is important to understand the molecular mechanisms that cause thyroid carcinoma, so as to find effective diagnostic and therapeutic targets. Aim of the study To explore the role of homeobox transcript antisense RNA (HOTAIR) in thyroid carcinoma through protein phosphatase methylesterase 1 (PPME1) by sponging microRNA 761 (miR‐761). Methods The regulation network amongst HOTAIR, miR‐761 and PPME1 was predicted by online sources. RT‐PCR was conducted to evaluate the expression of HOTAIR and miR‐761 in tumor tissues. Clinical data was collected and analyzed by Chi‐square test. Cell apoptosis and proliferation was evaluated using three types of cancer cells (HTh‐7, CAL‐62, BCPAP) after treated with si‐HOTAIR and miR‐761inhibitor. The binding site among HOTAIR, miR‐761 and PPME1 was verified by dual luciferase reporter assay. PPME1 expression was measured after HOTAIR and miR‐761 were suppressed by western blot. Survival time was measured in nude mice using log‐rank test. Results HOTAIR was expressed to a significantly greater extent than miR‐761 in thyroid tumor tissues (P < .001). miR‐761 and PPME1 were negatively correlated (coef = −1.91, P < .001). HOTAIR competitively binds to miR‐761 and miR‐761 directly targets PPME1. HOTAIR was highly correlated with TNM (χ2 = 5.797, P = .016), tumor size (χ2 = 7.955, P = .005) and lymphatic metastasis (χ2 = 6.0, P = .014). HOTAIR promoted cell proliferation and inhibited cell apoptosis, whereas miR‐761 did not. HOTAIR elevated and miR‐761 suppressed PPME1 expression. HOTAIR expression appears to affect the survival time in vivo. Conclusion HOTAIR regulated thyroid cancer cells by binding to miR‐761 through PPME1. HOTAIR regulated thyroid cancer cell by binding to miR‐761 through PPME1. From the clinical data, we found HOTAIR could be an independent predicted factor for thyroid tumor staging.